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Academic literature on the topic 'IL-1ra'

Author: Grafiati

Published: 4 June 2021

Last updated: 11 March 2023

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Journal articles on the topic "IL-1ra"

Powers, Nicholas E., Benjamin Swartzwelter, Carlo Marchetti, Dennis M. de Graaf, Alexandra Lerchner, Martin Schlapschy, Rajiv Datar, et al. "PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis." Journal of Biological Chemistry 295, no. 3 (December 9, 2019): 868–82. http://dx.doi.org/10.1074/jbc.ra119.010340.

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Interleukin-1 (IL-1) is a key mediator of inflammation and immunity. Naturally-occurring IL-1 receptor antagonist (IL-1Ra) binds and blocks the IL-1 receptor-1 (IL-1R1), preventing signaling. Anakinra, a recombinant form of IL-1Ra, is used to treat a spectrum of inflammatory diseases. However, anakinra is rapidly cleared from the body and requires daily administration. To create a longer-lasting alternative, PASylated IL-1Ra (PAS–IL-1Ra) has been generated by in-frame fusion of a long, defined-length, N-terminal Pro/Ala/Ser (PAS) random-coil polypeptide with IL-1Ra. Here, we compared the efficacy of two PAS–IL-1Ra molecules, PAS600–IL-1Ra and PAS800–IL-1Ra (carrying 600 and 800 PAS residues, respectively), with that of anakinra in mice. PAS600–IL-1Ra displayed markedly extended blood plasma levels 3 days post-administration, whereas anakinra was undetectable after 24 h. We also studied PAS600–IL-1Ra and PAS800–IL-1Ra for efficacy in monosodium urate (MSU) crystal-induced peritonitis. 5 days post-administration, PAS800–IL-1Ra significantly reduced leukocyte influx and inflammatory markers in MSU-induced peritonitis, whereas equimolar anakinra administered 24 h before MSU challenge was ineffective. The 6-h pretreatment with equimolar anakinra or PAS800–IL-1Ra before MSU challenge similarly reduced inflammatory markers. In cultured A549 lung carcinoma cells, anakinra, PAS600–IL-1Ra, and PAS800-IL-Ra reduced IL-1α–induced IL-6 and IL-8 levels with comparable potency. In human peripheral blood mononuclear cells, these molecules suppressed Candida albicans–induced production of the cancer-promoting cytokine IL-22. Surface plasmon resonance analyses revealed significant binding between PAS–IL-1Ra and IL-1R1, although with a slightly lower affinity than anakinra. These results validate PAS–IL-1Ra as an active IL-1 antagonist with marked in vivo potency and a significantly extended half-life compared with anakinra.

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Vannier, E., R. de Waal Malefyt, A. Salazar-Montes, JE de Vries, and CA Dinarello. "Interleukin-13 (IL-13) induces IL-1 receptor antagonist gene expression and protein synthesis in peripheral blood mononuclear cells: inhibition by an IL-4 mutant protein." Blood 87, no. 8 (April 15, 1996): 3307–15. http://dx.doi.org/10.1182/blood.v87.8.3307.bloodjournal8783307.

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Interleukin-13 (IL-13) belongs to the IL-4 gene family. Like IL-4, IL- 13 induces IL-1 receptor antagonist (IL-1Ra) synthesis with no effect on IL-1beta synthesis. We investigated whether IL-13 induces IL-1Ra synthesis via a pathway similar to IL-4. In human peripheral blood mononuclear cells, IL-13 (1 to 100 ng/mL alone induced IL-1Ra synthesis in a dose-dependent manner. A single amino acid mutant form of IL-4 (hIL4.Yl24D) induced IL-1Ra synthesis, acting as a partial agonist. However, hIL-4.Yl24D inhibited IL-1Ra synthesis induced by either IL-4 or IL-13. IL-13 alone induced accumulation of IL-1Ra mRNA. Furthermore, IL-13 reduced steady- state levels for IL-1beta mRNA but enhanced those for IL-1Ra mRNA in cells stimulated with lipopolysaccharide (LPS) or IL- 1alpha. Accordingly, IL-13 suppressed IL-1beta synthesis but enhanced IL-1Ra synthesis in these cells. IL-13 reduced the stability of IL- 1beta mRNA (2.9 v 1.7 hours) but failed to modify the stability of IL- 1Ra mRNA (2.7 v 2.5 hours). Moreover, IL-13 induced transcriptional activation of the IL-1Ra gene, but reduced IL-1beta gene transcription. Our results suggest that the commonality between IL-13 and IL-4 in inducing IL-1Ra synthesis results from the engagement of a subunit common to both receptors.

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Jordan, M., I. G. Otterness, R. Ng, A. Gessner, M. Röllinghoff, and H. U. Beuscher. "Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist." Journal of Immunology 154, no. 8 (April 15, 1995): 4081–90. http://dx.doi.org/10.4049/jimmunol.154.8.4081.

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Abstract IL-1 is a potent cytokine that promotes host defense and inflammation. These processes may be modulated by an IL-1 receptor antagonist (IL-1Ra) that binds to and blocks IL-1 receptors. The objective of this study was to define the cellular origin and regulation of IL-1Ra production during bacterial infection. Oral infection of mice with Yersinia enterocolitica resulted in expression of IL-1Ra mRNA and synthesis of IL-1Ra in Peyer's patches (PP), the local site of infection, as well as in noninfected organs such as spleens. By immunostaining, recruited circulating neutrophils were identified to be the primary source of IL-1Ra in tissues. Only approximately 20% of the IL-1Ra-staining cells were accounted for by inflammatory macrophages. Strikingly, neutralization of IL-6 by anti-IL-6 antiserum caused a suppression of both IL-1Ra mRNA in PP and synthesis of IL-1Ra in circulating neutrophils. Confirmatory evidence that IL-6 participates in the generation of IL-1Ra was obtained when rIL-6 induced, and anti-IL-6 antiserum blocked, IL-1Ra expression in cultures of macrophage and polymorphonuclear leukocytes (PMN). These findings suggest that IL-6 induced induction of IL-1Ra may provide a negative feedback loop, facilitating resolution of the inflammatory response locally and presumably at remote sites of infection.

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Levine, S. J., T. Wu, and J. H. Shelhamer. "Extracellular release of the type I intracellular IL-1 receptor antagonist from human airway epithelial cells: differential effects of IL-4, IL-13, IFN-gamma, and corticosteroids." Journal of Immunology 158, no. 12 (June 15, 1997): 5949–57. http://dx.doi.org/10.4049/jimmunol.158.12.5949.

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Abstract Three IL-1R antagonists (IL-1Ra) exist: secreted IL-1Ra and intracellular IL-1Ra (icIL-1Ra) types I and II. We have previously reported that human airway epithelial cells (HAEC) express icIL-1Ra type I, which can be up-regulated by corticosteroids. This study assessed whether cytokines and corticosteroids differentially effect icIL-1Ra type I protein release from HAEC to the extracellular compartment. We report that icIL-1Ra type I mRNA and intracellular protein are up-regulated in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, in response to IL-4, IL-13, IFN-gamma, and dexamethasone. The icIL-1Ra type I protein was detected in concentrated cell culture supernatants from NCI-H292 cells and normal human bronchial epithelial cells. The release of biologically relevant concentrations of active IL-1Ra from normal human bronchial epithelial cells was demonstrated by the ability of a neutralizing anti-IL-1Ra Ab to augment IL-1beta-mediated IL-8 secretion. IL-4, IL-13, and IFN-gamma induced immunoreactive IL-1Ra release into supernatants from NCI-H292 cells. Dexamethasone inhibited constitutive and cytokine-induced release of immunoreactive IL-1Ra. The release of icIL-1Ra type I protein was not related to cytotoxicity, as measured by lactate dehydrogenase. We propose that icIL-1Ra type I release from HAEC represents a novel mechanism by which IL-1 bioactivity in the airway microenvironment may be modulated. Cytokine-mediated icIL-1Ra type I synthesis may increase both intracellular protein and release to the extracellular space, where cell surface IL-1R can be antagonized. In contrast, corticosteroid-induced increases in icIL-1Ra type I synthesis and inhibition of extracellular protein release promote accumulation of icIL-1Ra type I protein within the intracellular compartment.

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Poutsiaka, DD, BD Clark, E. Vannier, and CA Dinarello. "Production of interleukin-1 receptor antagonist and interleukin-1 beta by peripheral blood mononuclear cells is differentially regulated." Blood 78, no. 5 (September 1, 1991): 1275–81. http://dx.doi.org/10.1182/blood.v78.5.1275.1275.

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Abstract We studied the relationship between the production of the 23-Kd interleukin-1 receptor antagonist (IL-1ra) and IL-1 beta in cultures of human peripheral blood mononuclear cells (PBMC) using a specific radioimmunoassay for IL-1ra that had a sensitivity of 166 +/- 11 pg/mL. PBMC cultured without human serum made little IL-1ra or IL-1 beta. In the presence of 1% AB serum, there was no increase in IL-1 beta (0.25 +/- 0.13 ng/mL) but IL-1ra production increased sevenfold to 3.4 +/- 0.5 ng/mL. IgG (2.5 to 100 micrograms/mL IgG) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 to 100 ng/mL) had no significant effect on IL-1 beta production but increased IL-1ra production up to 18- fold (18.2 +/- 3.9 ng/mL). Using endotoxin as a stimulant, 82% +/- 2% of IL-1ra was secreted in comparison with 52% +/- 9% of IL-1 beta. Culture conditions of PBMC influenced the production of IL-1ra but not IL-1 beta. Rocking endotoxin-stimulated PBMC produced 75% less IL-1ra but the same amount of IL-1 beta when compared with PBMC cultured in stationary plastic tubes. Rocking IgG-or GM-CSF-stimulated PBMC also produced 75% to 80% less IL-1ra. GM-CSF or IL-1 beta at concentrations that elicited submaximal production of IL-1ra potentiated IgG-induced IL-1ra production. The production of IL-1ra and IL-1 beta are under differential regulation because serum, IgG, and GM-CSF were potent stimuli for the production of IL-1ra but not IL-1 beta, and the prevention of cell-cell contact of PBMC reduced IL-1ra but not IL-1 beta production.

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We studied the relationship between the production of the 23-Kd interleukin-1 receptor antagonist (IL-1ra) and IL-1 beta in cultures of human peripheral blood mononuclear cells (PBMC) using a specific radioimmunoassay for IL-1ra that had a sensitivity of 166 +/- 11 pg/mL. PBMC cultured without human serum made little IL-1ra or IL-1 beta. In the presence of 1% AB serum, there was no increase in IL-1 beta (0.25 +/- 0.13 ng/mL) but IL-1ra production increased sevenfold to 3.4 +/- 0.5 ng/mL. IgG (2.5 to 100 micrograms/mL IgG) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 to 100 ng/mL) had no significant effect on IL-1 beta production but increased IL-1ra production up to 18- fold (18.2 +/- 3.9 ng/mL). Using endotoxin as a stimulant, 82% +/- 2% of IL-1ra was secreted in comparison with 52% +/- 9% of IL-1 beta. Culture conditions of PBMC influenced the production of IL-1ra but not IL-1 beta. Rocking endotoxin-stimulated PBMC produced 75% less IL-1ra but the same amount of IL-1 beta when compared with PBMC cultured in stationary plastic tubes. Rocking IgG-or GM-CSF-stimulated PBMC also produced 75% to 80% less IL-1ra. GM-CSF or IL-1 beta at concentrations that elicited submaximal production of IL-1ra potentiated IgG-induced IL-1ra production. The production of IL-1ra and IL-1 beta are under differential regulation because serum, IgG, and GM-CSF were potent stimuli for the production of IL-1ra but not IL-1 beta, and the prevention of cell-cell contact of PBMC reduced IL-1ra but not IL-1 beta production.

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Watson, J. M., A. K. Lofquist, C. A. Rinehart, J. C. Olsen, S. S. Makarov, D. G. Kaufman, and J. S. Haskill. "The intracellular IL-1 receptor antagonist alters IL-1-inducible gene expression without blocking exogenous signaling by IL-1 beta." Journal of Immunology 155, no. 9 (November 1, 1995): 4467–75. http://dx.doi.org/10.4049/jimmunol.155.9.4467.

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Abstract The epithelium-associated tissue distribution of the intracellular IL-1R antagonist (icIL-1Ra) suggests that it functions as a novel regulatory molecule for IL-1 in somatic tissues. We examined the role of the icIL-1Ra in IL-1 beta-induced responses in human ovarian cancer cells because ovarian surface epithelium expresses transcripts for the icIL-1Ra, and the majority of ovarian cancers arise from these cells. Several human ovarian and cervical cancer cell lines spontaneously express the icIL-1Ra. icIL-1Ra-expressing cells did not have altered growth characteristics or altered short term responses to IL-1 compared with icIL-1Ra-nonexpressing cells. While a 90-min exposure to IL-1 beta resulted in increased steady state cytokine mRNA levels in all cells, icIL-1Ra-positive cells were incapable of maintaining IL-1-beta-induced expression of GRO mRNA. This did not result from decreased transcriptional activity of the GRO gene, but reflected differences in mRNA stability and/or degradation. To determine whether the icIL-1Ra altered mRNA stability, we used a retroviral expression vector to express the icIL-1Ra in an icIL-1Ra-negative cell line. The resulting cells displayed a profile of IL-1 beta-induced genes analogous to that found in cells spontaneously expressing icIL-1Ra. These data show for the first time an intrinsic biologic activity for the icIL-1Ra. The capacity to selectively alter IL-1-induced gene expression suggests that this version of the IL-1Ra is a unique intracellular inhibitor that attenuates IL-1 responses at a point downstream of the initial IL-1/IL-1 receptor interaction.

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Chomarat, P., E. Vannier, J. Dechanet, M. C. Rissoan, J. Banchereau, C. A. Dinarello, and P. Miossec. "Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its regulation by IL-4 and IL-10." Journal of Immunology 154, no. 3 (February 1, 1995): 1432–39. http://dx.doi.org/10.4049/jimmunol.154.3.1432.

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Abstract The spontaneous production of IL-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) by rheumatoid arthritis (RA) synovium, and the regulation of their production by IL-4 and IL-10, were studied. Supernatants from cultured synovium pieces from 19 RA patients were assayed for IL-1 beta and IL-1Ra production using ELISA and RIA, respectively. After 10 days of culture, spontaneous production of IL-1Ra was 1.42 +/- 0.43 ng/ml/100 mg of synovium whereas spontaneous production of IL-1 beta was 4.03 +/- 0.90 ng/ml/100 mg of synovium (n = 19). The addition of IL-4 reduced IL-1 beta production by 2.3-fold (p = 0.001) and increased that of IL-1Ra by 2.8-fold (p = 0.003). IL-10 had no significant effect on IL-1Ra production and suppressed IL-1 beta production (primarily in samples producing high levels of IL-1 beta). However, IL-10 was less potent than IL-4 in suppressing IL-1 beta production. IL-1Ra was mainly produced by rheumatoid synovial monocytes/macrophages. IL-4 was more potent than IL-10 in inducing IL-1Ra production by monocytes/macrophages purified from RA synovium, as well as from RA blood. Thus, RA synovium is characterized by an imbalance between IL-1Ra and IL-1 beta production, in favor of the latter. IL-4, and to a lesser extent IL-10, shift this balance in favor of an anti-inflammatory situation.

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Roberge, C. J., R. de Médicis, J. M. Dayer, M. Rola-Pleszczynski, P. H. Naccache, and P. E. Poubelle. "Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist." Journal of Immunology 152, no. 11 (June 1, 1994): 5485–94. http://dx.doi.org/10.4049/jimmunol.152.11.5485.

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Abstract Neutrophils produce IL-1 when stimulated by monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals. Neutrophils also generate the IL-1R antagonist (IL-1Ra), especially when incubated with granulocyte-macrophage CSF (GM-CSF) or TNF-alpha. We studied the simultaneous expression of IL-1 and IL-1Ra by GM-CSF- or TNF-alpha-treated neutrophils activated by MSU or CPPD. Neutrophils incubated with GM-CSF or TNF-alpha produced approximately 300 or 200 times more IL-1Ra than IL-1, respectively. Suboptimal concentrations of MSU or CPPD induced low amounts of IL-1 without affecting IL-1Ra. Interaction of GM-CSF- and TNF-alpha-treated neutrophils with MSU or CPPD up-regulated IL-1 while simultaneously down-regulating IL-1Ra. As a result, the bioactivity of IL-1 secreted was enhanced. Synergistic increases of IL-1 (but not IL-1Ra) mRNA levels were noted in GM-CSF- or TNF-alpha-treated neutrophils exposed to CPPD. Treatment of neutrophils with colchicine before incubation with GM-CSF or TNF alpha, inhibited crystal-induced IL-1 by 50 to 55%, but failed to significantly affect IL-1Ra. The IL-1Ra to IL-1 ratio was significantly increased by 185 to 220%. These results demonstrate that IL-1 and IL-1Ra production by human neutrophils are differentially regulated, that the combined presence of GM-CSF or TNF-alpha and microcrystals favor the production of biologically active IL-1 over that of IL-1Ra, and that colchicine selectively inhibits IL-1 without affecting IL-1Ra production.

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Yoon, Ho Joo, Zhou Zhu, Jack M. Gwaltney, and Jack A. Elias. "Rhinovirus Regulation of IL-1 Receptor Antagonist In Vivo and In Vitro: A Potential Mechanism of Symptom Resolution." Journal of Immunology 162, no. 12 (June 15, 1999): 7461–69. http://dx.doi.org/10.4049/jimmunol.162.12.7461.

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Abstract Rhinovirus (RV) upper respiratory tract infections are prototypic transient inflammatory responses. To address the mechanism of disease resolution in these infections, we determined if RV stimulated the production of the IL-1 receptor antagonist (IL-1ra) in vivo and in vitro. In contrast to IL-1α and IL-1β, immunoreactive IL-1ra was readily detected in the nasal washings of normal human volunteers. Symptomatic RV infection caused a small increase in IL-1α, a modest increase in IL-1β, and an impressive increase in IL-1ra. Maximal induction of IL-1α and IL-1β was transiently noted 48 h after RV infection. In contrast, maximal induction of IL-1ra was prolonged appearing 48–72 h after RV infection. These time points corresponded to the periods of peak symptomatology and the onset of symptom resolution, respectively. Western analysis of nasal washings demonstrated that RV stimulated the accumulation of intracellular IL-1ra type I in all and secreted IL-1ra in a subset of volunteers. Unstimulated normal respiratory epithelial cells contained intracellular IL-1ra type I mRNA and protein. RV infection increased the intracellular levels and extracellular transport of this IL-1ra moiety without causing significant changes in the levels of IL-1ra mRNA. IL-1ra may play an important role in the resolution of RV respiratory infections. RV stimulates epithelial cell IL-1ra elaboration, at least in part, via a novel translational and/or posttranslational mechanism.

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Dissertations / Theses on the topic "IL-1ra"

COLANTUONI, MARIASILVIA. "Sviluppo preclinico di terapia genica basato sull'espressione di IL-1RA per il trattamento di malattia autoinfiammatorie." Doctoral thesis, Università Vita-Salute San Raffaele, 2022. http://hdl.handle.net/20.500.11768/133061.

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Le malattie autoinfiammatorie sistemiche si manifestano quando il sistema immunitario viene attivato in maniera incontrollata. Un sottogruppo cardinale di queste malattie comprende rare febbri periodiche caratterizzate dalla produzione disregolata della citochina proinfiammatoria interleuchina-1 (IL-1). Non esiste una cura per queste condizioni. Anakinra, il farmaco rappresentante la ricombinante dell'antagonista del recettore IL-1 (IL-1RA), è la terapia principale per questi pazienti. Tuttavia, l’anakinra ha una breve emivita e una scarsa distribuzione dei tessuti. I pazienti gravi rispondono in modo inadeguato e i loro sintomi non migliorano. Pertanto, è necessaria una terapia duratura che oltrepassi la somministrazione continua di farmaci e garantisca una risoluzione soddisfacente dell'infiammazione dei tessuti. In questo progetto di dottorato, abbiamo affrontato l'urgenza di sviluppare un trattamento efficace per queste malattie, basato su cellule staminali ematopoietiche che producono costitutivamente la proteina umana IL-1RA utilizzando un approccio di trasferimento genico mediato da vettori lentivirali (LV). Abbiamo dimostrato che le cellue staminali trasdotte producono in maniera efficace I-1RA. Il protocollo di trasduzione associato alla sovraespressione di IL-1RA non hanno alterato la vitalità cellulare, il potenziale clonogenico e l’abilità delle cellule staminali di differenziazione nel topo. Successivamente, abbiamo studiato se le cellule staminali esprimenti IL-1RA, una volta trapiantate nei topi potessero migliorare l'infiammazione acuta e cronica. Sono stati impiegati tre modelli di topi. L'espressione ectopica di IL-1RA da parte delle cellule immunitarie derivate dalle cellule staminali trapiantate ha soppresso il reclutamento dei neutrofili nel sito dell'infiammazione nei topi con peritonite indotta da cristalli di urato monosodico (MSU), noti attivatori del complesso NLRP3 dell’inflammasoma. Questo effetto protettivo era paragonabile a quello ottenuto da anakinra. Successivamente, abbiamo sfruttato un modello murino inducibile esprimente la mutazione dominante Nlrp3A350V associata alle sindromi periodiche associate alla criopirina (CAPS). Il trapianto singenico di cellule staminali trasdotte con IL-1RA in topi Nlrp3A350V+CreT ha efficacemente impedito ai topi l'insorgenza e la progressione della malattia associata a perdita di peso, leucocitosi e livelli sierici elevati dell’interleuchina 6. Infine, i nostri dati preliminari indicano che il nostro approccio di terapia genica potrebbe migliorare il tasso di mortalità e la gravità della malattia in un modello murino di encefalomielite autoimmune sperimentale. Complessivamente, i nostri risultati hanno dimostrato che la somministrazione di IL-1RA mediata da un vettore lentivirale nelle cellule staminali è un approccio sicuro ed efficiente per controllare l'infiammazione mediata da IL-1. Questi risultati hanno posto le basi per studi futuri per valutare la potenziale applicazione clinica della tarapia genica con IL-1RA per le malattie autoinfiammatorie sistemiche mediate da IL-1.
Systemic autoinflammatory diseases (SAIDs) delineate a group of diseases that manifest when the immune system is activated uncontrollably. One cardinal subgroup of SAIDs includes rare periodic fevers characterized by the dysregulated production of the proinflammatory cytokine interleukin-1 (IL-1). There is no cure for these conditions. Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1RA), is the mainstay therapy for these patients. However, anakinra has a short half-life and poor tissue distribution. Severe patients respond inadequately and do not experience improvement in symptoms. Therefore, there is a need for a durable therapy that bypasses continuous drug administration and ensures a satisfactory resolution of tissue inflammation. In this PhD project, we addressed the urgency to develop an effective treatment for IL-1 induced SAIDs based on haematopoietic stem and progenitor cells (HSPCs) producing constitutively human IL-1RA using a lentiviral vector (LV)-mediated gene transfer approach. Human and mouse HSPCs transduced with an LV encoding human IL-1RA efficiently released this cytokine. Transduction procedure and IL-1RA over-expression did not alter HSPCs viability, clonogenic and differentiation potential in vivo. Next, we investigated whether, once transplanted in mice, IL-1RA-expressing HSPCs could ameliorate acute and chronic inflammation. Three mouse models were employed. The ectopic expression of IL-1RA by HSPC-derived immune cells suppressed neutrophil recruitment to the site of inflammation in mice with peritonitis induced by monosodium-urate crystals (MSU), well-known activators of the NLRP3-IL-1 axis. This protective effect was comparable to that obtained by anakinra. Next, we exploited an inducible mouse model of the cryopyrin-associated period syndrome (CAPS) carrying the dominant Nlrp3A350V mutation. Syngeneic transplant of IL-1RA-transduced HSPCs in Nlrp3A350V+CreT mice effectively prevented mice from disease onset and progression manifested as weight loss, leucocytosis, and high serum IL-6 level. Finally, preliminary data indicate that our gene therapy approach could improve mortality rate and disease severity in a mouse model of experimental autoimmune encephalomyelitis. Altogether, our results demonstrated that LV-mediated IL-1RA delivery in HSPCs is safe and efficient approach to controlling IL-1-mediated inflammation. These findings set the stage for future studies to evaluate the potential LV-mediated IL-1RA GT clinical application for IL-1-mediated systemic autoinflammatory diseases.

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Caslin, Heather. "The Effect of Obesity on IL-1β, IL-1Ra, and Leptin Following Acute Mental Stress." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/600.

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Research regarding the development of cardiovascular disease (CVD) is important because CVD is the leading cause of death in the United States (US) and many countries abroad. Risk factors, such as obesity and psychological stress, should be studied in order to understand contributing factors for CVD and the cellular mechanisms which link risk factors with the development of disease. Specifically, the combined influence of multiple risk factors on inflammation is of interest because many individuals have more than one risk factor, which additively increases an individual’s risk for CVD. Obesity is already characterized by disordered inflammation, which suggests that the additional burden of a psychological stressor could elicit a greater inflammatory response and a greater risk for CVD than either stressor alone. The documents included within this thesis include the significance and specific aims of the study in addition to a review of the relevant literature related to the effects of obesity and acute mental stress (AMS) on endocrine and inflammatory markers. Specifically, this study aims to address IL-1β, IL-1Ra, and leptin following an AMS task in non-obese and obese individuals. Additionally, a manuscript is included which evaluates the change in IL-1β, IL-1Ra, and leptin following a 20 minute AMS task. Variables were examined between groups at baseline and at two time points following AMS. Additionally, the relationships among the changes in the markers following AMS were examined. Appendices include expanded methodology and all questionnaires used.

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Moreira, Juliana Junqueira. "Avaliação dos efeitos da utilização de plasma autólogo condicionado em articulações sinoviais hígidas de equinos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-06122013-142533/.

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O cavalo tem sido há milhares de anos um dos animais de maior utilidade para o homem, tanto no trabalho quanto no esporte. A integridade de sua estrutura física é determinante para a qualidade de seu desempenho, sendo alvo importante das estratégias terapêuticas e preventivas da atualidade. Diversos estudos têm esclarecido parte da cascata de eventos que ocorre em ambiente intra-articular, revelando os principais mediadores nocivos e ampliando as opções para tratamentos mais eficientes. Experimentos utilizando a citometria de fluxo foram capazes de demonstrar que a adição de plasma às células de líquido sinovial (LS) previamente inflamadas diminui a produção de espécies reativas de oxigênio durante o burst oxidativo, conferindo capacidade antioxidante a este hemoderivado. Pouco se sabe, no entanto, sobre seu potencial pró ou anti-inflamatório, pois não existem relatos na literatura investigando tal atividade. Assim, desenvolvemos este estudo com o objetivo de acompanhar os efeitos exercidos pelo plasma autólogo condicionado (ACP) sobre os tecidos articulares, reportando as alterações clínicas e no LS das articulações metacarpofalangeanas hígidas que receberam este tratamento. Foram administrados 4 ml de ACP em 10 articulações metacarpofalangeanas de equinos saudáveis, enquanto as articulações contralaterais receberam 4 ml de solução fisiológica, como controle. LS foi coletado antes de cada aplicação e nos momentos 3, 6, 24, 48 e 168 horas após. Foi realizada avaliação física diária, e as amostras coletadas foram submetidas imediatamente a análise física (volume, cor, aspecto e viscosidade), teste da qualidade do precipitado de mucina, contagem total e diferencial das células nucleadas. O sobrenadante foi congelado para dosagem posterior de ureia, proteína total, ácido hialurônico (AH), condroitim sulfato (CS), prostaglandina E2 (PGE2) e das citocinas fator de necrose tumoral alfa (TNF-α), interleucina 1 beta (IL-1β) e antagonista do receptor de IL-1 (IL-1ra). A avaliação física dos animais detectou presença de claudicação nas articulações metacarpofalangeanas tratadas com ACP nos momentos 24 e 48 horas após sua administração. A análise física do LS das mesmas articulações revelou maior contaminação das amostras com sangue às 6 horas e maior contagem de células nucleadas às 3, 6, 24 e 48 horas, com predomínio de leucócitos polimorfonucleares. Ainda, o ACP induziu maiores concentrações de proteína total e PGE2 às 3 e 6 horas, e maior concentração de CS às 24 horas. Houve também tendência ao aumento de TNF-α às 24 horas. Às 168 horas, todavia, nenhuma alteração foi observada em quaisquer dos itens avaliados. Não ocorreram alterações nos demais aspectos físicos do LS nem na qualidade do precipitado de mucina, tampouco nas concentrações de ureia e AH. Estes resultados indicam que em articulações hígidas o ACP possui ação pró-inflamatória transitória, com maiores concentrações de PGE2 induzindo o catabolismo dos PGs da matriz, aumentando particularmente o CS.
History has connected human and equine species, for work and pleasure purposes and in both scenarios, horses\' physical integrity is of paramount importance for adequate performance. Soundness has been the target of many studies in orthopedic therapeutics and preventive equine medicine. Several of these studies have thrown light on the sequence of deleterious intra-articular events that take place after an insult, revealing key mediators of joint destruction and widening treatment options. Experiments evaluating the effects of plasma on reactive oxygen species production by chemically stimulated synovial fluid (SF) cells revealed a potent antioxidant effect. Little is known, however about plasma´s anti or pro inflammatory activities, still an unexplored property of plasma. This study was to designed to observe the effects of autologous conditioned plasma (ACP) on articular components, reporting findings of serial SF analysis and clinical evaluations, before and after its administration in healthy metacarpophalangeal joints. Four mililiters of ACP were injected in 10 healthy metacarpophalangeal joints, and the contralateral joints were injected with 4 ml of saline, serving as controls. SF was obtained for analysis before, and then 3, 6, 24, 48 and 168 hours after treatment injection. Horses were subjected to daily clinical evaluations and synovial fluid samples were immediately analyzed for color, viscosity, volume, aspect, quality of mucin clot and total and differential nucleated cell counts. The supernatant was frozen and stored for posterior dosages of urea, total protein, hyaluronic acid (HA), chondroitin sulphate (CS), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL- 1β), and interleukin 1 receptor antagonist (IL-1ra). Physical evaluation of ACP treated subjects detected mild lameness at 24 and 48 hours observation points. SF analysis of ACP treated joints revealed blood contamination and higher total nucleated cell counts at 3, 6, 24 and 48 hours, with predominance of polymorphonuclear cells. ACP treatment has also induced higher protein concentrations and PGE2 levels at 3 and 6 hours and higher CS levels at 24 hours in synovial fluid analysis. At 24 hours, TNFα concentrations were higher, although not significantly. At 168 hours post ACP treatment, however, no change was observed in any parameter of synovial fluid analysis. No alterations were detected in the remaining items evaluated, nor in the quality of the mucin clot, urea concentration or HA. These results indicate that, when injected into healthy joints, ACP elicits a transient inflammatory response, characterized by higher PGE2 concentrations, matrix catabolism, with particular increase in CS.

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Amabile, Gerardo. "SVILUPPO DI SISTEMI MICROPARTICELLARI PER IL RILASCIO INTRAARTICOLARE PROLUNGATO DI CITOCHINE ANTIINFIAMMATORIE PER LA TERAPIA DELLE PATOLOGIE REUMATICHE." Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3427552.

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Purpose: The aim of our study is to develop a long lasting biotech drug delivery system for intraartcular (IA) treatment of rheumatic diseases as rheumatoid arthritis and osteoarthritis. The study was focused on preparation of microparticles formulated with biocompatible/biodegradable polymers (PLGA and PLA). Recombinant Human IL-1Ra was used as biotechnological drug model. Introduction: Polymeric microparticles have been widely studied as drug delivery systems for biotech drugs. These formulation can guarantee long term stability of the drug and sustained release allowing for therapeutic protocol optimisation. Nevertheless, protein formulation is usually complicated by the low stability of these fragile molecules which easily undergo denaturation and inactivation under harsh manipulation conditions. The set up of proper procedures which preserve the protein activity is essential to achieve effective products. Experimental: In the present research work, the preparation of biodegradable polymeric microparticles was investigated by using several techniques: emulsion/evaporation, double emulsion/evaporation, suspension/evaporation, nanoprecipitation, spray-drying. In a systematic study, various excipient combinations (PLA, PLGA, PLGAH, PEG, Tristearin, Hyaluronic Acid, Poloxamers etc.) and operative conditions (polymer and protein concentration, instrument set up etc.) were evaluated in order to point out the main critical parameters which dictate the physicochemical properties of the preparations. The products were characterised for their morphological and dimensional properties, drug loading and release were assessed. In vitro release of Il-1Ra from microparticles was evaluated by suspension in buffer and synovial fluid using RP-HPLC and ELISA methods. Pharmacokinetic of IL-1Ra was studied in mice using ELISA methods. Therapeutic efficacy of IL-1Ra loaded microspheres was tested using an animal model of collagen inducted arthritis. Results: Many kind of formulations were obtained using different kind of biocompatible polymers, different ratios between components, different polymers concentrations and procedures of preparation. Spray-drying techniques were the most efficient as they achieved for product yeld, drug loading and narrow dimensional polydispersivity. The preparation of protein suspensions in organic solvent solution of PLA or PLGA and PEG yielded microparticles with size ranging from 1 to 30 m which were suitable for IA administration. The main critical parameters affecting the biopharmaceutical properties of the formulations were: PEG molecular weight and content in the organic solution, PLA or PLGA concentration in the organic solution, type of PLGA and spray feed rate. Under optimized conditions, spherical and homogeneous microparticles in a size range between 2 and 15m were obtained with about 70% drug loading; the microspheres were formed by PLGA (75%), Epikuron 200SH (5%), PEG 5kDa (10%) and IL-Ra (10%). Pharmacokinetic studies demonstrated that microsphere formulation permitted a prolonged in vivo release of IL-1Ra. The use of animal model of collagen inducted arthritis underlined that the injection of IL-1Ra loaded microspheres permits the reduction of Anakinra treatment rate. Conclusion: Spray Drying is a suitable method to obtain drug delivery systems for the prolonged release of biotechnological products such as cytokines and monoclonal antibodies. The physicochemical properties of the products can be tailored by changing different process conditions and formulation composition.
Scopo: Lo scopo di questo studio è stato quello di sviluppare un sistema a rilascio prolungato per il delivery di farmaci biotecnologici per il trattamento intraarticolare (IA) delle patologie infiammatorie croniche come l’artrite reumatoide e l’osteoartrosi. Lo studio è stato focalizzato sulla preparazione di microparticelle costituite da polimeri biodegradabili e biocompatibili (PLGA, PLA e derivati dell’acido ialuronico). IL-1Ra umano ricombinante (anakinra) è stato utilizzato come modello di farmaco biotecnologico ad azione antiinfiammatoria per il suo ruolo fondamentale di antagonista del recettore per l’IL-1, citochina della quale è noto il ruolo chiave proinfiammatorio nelle patologie reumatiche croniche. Introduzione: Le microparticelle polimeriche sono state ampiamente studiate come sistemi di drug delivery per i farmaci biotecnologici. Questo tipo di formulazioni può garantire la stabilità nel tempo del farmaco e un lento rilascio che consente di ottimizzare il protocollo terapeutico. Tuttavia, la formulazione di proteine è solitamente complicata dalla scarsa stabilità di queste fragili molecole che vanno incontro a denaturazione ed inattivazione se sottoposte a condizioni operative drastiche. La messa a punto di opportune procedure che conservino l’attività delle proteine è essenziale per ottenere prodotti efficaci. Materiali e Metodi: La preparazione di microparticelle a base di polimeri biodegradabili è stata studiata utilizzando diverse tecniche: nanoprecipitazione, emulsione ed estrazione della fase interna, emulsione ed evaporazione, doppia emulsione ed evaporazione, spray drying. Varie combinazioni di eccipienti (PLA, PLGA, PLGA-H, PEG, tristearina, acido ialuronico e derivati, Polossamero, fosfatidilcolina) e diverse condizioni operative (concentrazione del polimero e della proteina, settaggio della strumentazione ecc) sono state valutate al fine di evidenziare i principali parametri critici che determinano le proprietà chimico-fisiche della preparazione. I prodotti sono stati caratterizzati per le loro proprietà morfologiche e dimensionali, e sono stati valutati il caricamento e il rilascio del farmaco. Il rilascio in vitro di IL-1RA dalle microparticelle in tampone fisiologico o liquido sinoviale è stato valutato utilizzando tecniche come RP-HPLC ed ELISA. La cinetica di rilascio in vivo di IL-1Ra dalle microsfere è stata valutata mediante metodi ELISA. Sono stati effettuati degli studi di efficacia terapeutica della formulazione utilizzando un modello animale di artrite da collagene (C.I.A.); i diversi gruppi di animali sono stati trattati con diverse dosi di microsfere o di Kineret, e con frequenze diverse di somministrazione. Sono stati valutati il paw score, il peso, diametro dell’articolazione della caviglia e la tumefazione del femore. Risultati: Sono stati ottenute tipologie differenti di formulazioni utilizzando diversi tipi di polimeri biocompatibili, diversi rapporti tra i componenti, diverse concentrazioni di polimero e differenti procedure di preparazione. La tecnica di spray drying è risultata la più efficace in termini di resa, di caricamento del farmaco e di polidispersività dimensionale. La preparazione mediante spray drying di microsfere a partire da sospensioni di liofilizzati di IL-1Ra/PEG in soluzioni organiche di PLA o PLGA ha permesso l’ottenimento di microparticelle con dimensioni comprese tra 1 e 30m, compatibili con l’uso iniettabile. Si è verificato che i principali parametri critici che possono influenzare le proprietà biofarmaceutiche delle formulazioni sono: peso molecolare del PEG utilizzato e rapporto PEG/IL-1Ra nel liofilizzato, concentrazione di PLA o PLGA nel solvente organico, tipo di PLGA e velocità di alimentazione dell’ugello dello strumento. L’ottimizzazione di questi parametri ha permesso di ottenere microsfere di dimensioni adatte all’iniezione intraarticolare (2-15m) e con un elevata efficienza di caricamento del farmaco (50-70%); queste microparticelle sono costituite da 75% p/p di PLGA (in soluzione organica al 4%), 5% p/p di Epikuron 200SH (fosfatidilcolina), 10% p/p di PEG 5kDa e 10% p/p di IL-1Ra. Gli studi di farmacocinetica in topi Balb/c hanno evidenziato che, negli animali trattati con microsfere caricate con citochina, la concentrazione plasmatica di IL-1Ra decresce molto più lentamente che negli animali trattati con il prodotto commerciale Kineret® (anakinra); dopo 24h dalla somministrazione di Kineret, infatti, non vi è più traccia rilevabile di IL-1Ra nel plasma, mentre, dopo somministrazione di microsfere caricate con IL-1Ra, si rileva presenza di citochina per tempi superiori alle 48h. L’utilizzo del modello animale di artrite sperimentale ha permesso di valutare l’efficacia terapeutica delle microsfere: la somministrazione di microsfere caricate con IL-1Ra consente di ridurre la frequenza di trattamento ottenendo risultati confrontabili ad una iniezione giornaliera di Kineret. Conclusione: Il metodo di sospensione e spray drying sviluppato è adatto all’ottenimento di sistemi per il rilascio prolungato di prodotti biotecnologici come citochine, anticorpi monoclonali e proteine di fusione. Le caratteristiche chimico-fisiche dei prodotti possono essere modificate e adattate allo scopo desiderato variando le condizioni di processo e la composizione della formulazione.

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Zaliavska, O. V. "Diagnostic value of investigation of IL-1β, IL-4, IL-6, IF-γ, TNF-α and IL-1Ra content in the blood serum in reactive arthritis patients of different etiology." Thesis, БДМУ, 2017. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17051.

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Zalіavska, O. V. "Diagnostic value of investigation of IL-1β, IL-4, IL-6, IF-γ, TNF-α AND IL-1Ra content in the blood serum in reactive arthritis patients of different etiology." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18604.

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Böhm, Jasper [Verfasser], Wolfram [Gutachter] Teske, and Roland Ernst [Gutachter] Willburger. "Beeinflussung von lumbalem Bandscheibenprolapsgewebe durch IL-1Ra : eine vergleichende experimentelle Studie / Jasper Böhm ; Gutachter: Wolfram Teske, Roland Ernst Willburger ; Medizinische Fakultät." Bochum : Ruhr-Universität Bochum, 2018. http://d-nb.info/1154307743/34.

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Tellez, i. Besolí Noèlia. "Sobreexpressió de l'Antagonista del Receptor d'Interleucina 1 (IL-1Ra) en els illots pancreàtics .Efectes sobre viabilitat, funció i regeneració de les cèl·lules beta." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/1090.

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El trasplantament d'illots pancreàtics és una teràpia emergent per la curació de la diabetis mellitus. Una de les limitacions radica en la baixa disponibilitat d'òrgans i l'elevada demanda existent, que queda agreujada amb l'elevat nombre d'illots que són necessaris per restablir la normoglucèmia del pacient. Estudis recents del nostre grup, han mostrat que en els primers dies després del trasplantament hi ha un augment de l'expressió d'IL-1beta en els empelts d'illots.

La hipòtesi de treball és que la citocina proinflamatòria, IL-1, està implicada en la fallada del trasplantament. Designant la sobreexpressió d'IL-1Ra com l'estratègia a seguir per millorar el pronòstic del trasplantament singènic d'illots pancreàtics. Per tant, l'objectiu general de l'estudi va ser determinar si la sobreexpressió d'IL-1Ra en els illots pancreàtics protegeix les cèl·lules beta pancreàtiques dels efectes deleteris d'IL-1 en els illots i millora el pronòstic del trasplantament.

L'estudi dels efectes d'IL-1beta i de la sobreexpressió d'IL-1Ra in vitro es va realitzar amb un cultiu primari d'illots de rata que van ser exposats durant 48h a 5.5 o 22.2 mM de glucosa en presència o absència de 50U/ml d'IL-1beta. I la inserció del gen exogen a les cèl·lules dels illots es va fer utilitzant un adenovirus V recombinant.

La proliferació de les cèl·lules beta (determinada per incorporació de BrdU) va disminuir dràsticament quan es van exposar els illots a 50 U/ml d'IL-1beta, tant a 5.5 mM com a 22.2 mM de glucosa. Aquest efecte d'IL-1beta va quedar completament abolit per la sobreexpressió d'IL-1Ra en els illots que havien estat infectats amb l'adenovirus que codificava per l'antagonista, a les dues concentracions de glucosa utilitzades.

L'apoptosi de les cèl·lules beta (determinada per immunohistoquímica mitjançant la tècnica del TUNEL i per citometria de flux, marcant les cèl·lules amb anexina V i iodur de propidi) estava significativament augmentada en els illots exposats a IL-1beta, però no en els illots que sobreexpressaven IL-1Ra.

L'estudi dels efectes de la sobreexpressió d'IL-1Ra en els illots trasplantats es va realitzar utilitzant un model de trasplantament singènic. Grups de 500 illots control (no infectats) o que sobreexpressaven IL-1Ra van ser trasplantats sota la càpsula renal de rates Lewis diabètiques. 500 illots són una massa beta clarament insuficient per restablir la normoglucèmia, així doncs els animals d'ambdós grups es van mantenir hiperglucèmics durant tot l'estudi. Els empelts es van recuperar després de 3, 10 i 28 dies del trasplantament i es van processar per fer estudis histològics.

La sobreexpressió d'IL-1Ra en els illots trasplantats va fer augmentar significativament la proliferació de les cèl·lules beta dels empelts de 3, 10 i 28 dies i va protegir parcialment les cèl·lules beta de l'increment d'apoptosi detectat després del trasplantament, tant a curt com a llarg termini. L'àrea individual de les cèl·lules beta estava augmentada de manera similar tant en els empelts d'illots control com en els illots que sobreexpressaven IL-1Ra als 10 i 28 dies d'evolució. Finalment, la sobreexpressió d'IL-1Ra resultà en una recuperació de la massa beta inicialment trasplantada.

Per tal d'estudiar si els efectes beneficiosos de la sobreexpressió d'IL-1Ra aconseguien reduir el nombre d'illots necessaris per restablir la normoglucèmia, es va trasplantar una massa beta marginal (800 illots) d'illots control i Ad-IL-1Ra a animals diabètics. El 100% dels animals trasplantats amb illots Ad-IL-1Ra eren normoglucèmics després de 14 dies del trasplantament i només un 40% dels animals trasplantats amb illots control assoliren l'euglucèmia en aquest dia.

En aquest treball es mostra que la citocina proinflamatòria IL-1beta indueix clarament apoptosi a les cèl·lules beta dels illots de rata en cultiu i inhibeix dràsticament la replicació d'aquestes cèl·lules. La sobreexpressió d'IL-1Ra protegeix les cèl·lules beta dels efectes deleteris d'aquesta citocina i amplifica la resposta replicativa de les cèl·lules beta exposades a concentracions altes de glucosa. La sobreexpressió d'IL-1Ra en els illots augmenta la replicació de les cèl·lules beta trasplantades, les protegeix de l'apoptosi induïda després del trasplantament, i preserva la massa beta inicialment trasplantada. Els efectes beneficiosos de la sobreexpressió d'IL-1Ra observats en els illots trasplantats permeten reduir el nombre d'illots necessaris per restablir la normoglucèmia dels animals diabètics.

Aquests resultats suggereixen que la IL-1 juga un paper important en l'evolució dels empelts d'illots, ja que el seu bloqueig implica una millora dels illots trasplantats.
BACKGROUND AND AIMS:

IL-1beta could contribute to the dramatic beta cell loss that takes place after islet transplantation. It is known that exposure to sustained hyperglycemia has a deleterious effect on transplanted islets. Moreover, it has been recently reported that IL-1beta expression is increased in islets exposed to high glucose levels. IL-1Ra is a naturally occurring inhibitor of IL-1 action and its overexpression protects pancreatic islets from the deleterious effects of IL-1â on beta cell replication, apoptosis and function. The aim of this study was to determine whether viral gene transfer of the IL-1Ra gene into rat islets ex vivo could have a beneficial effect on beta cell replication and mass of transplanted islets.

METHODS:

Lewis rat islets were infected for 2h with 6.25 × 106 pfu of Ad-IL-1Ra and streptozotocin-diabetic Lewis rats were transplanted with 500 Ad-IL-1Ra infected islets (Ad-IL-1Ra group) or 500 uninfected islets (control group) under the kidney capsule. Grafts were removed 3 (n = 12), 10 (n = 12) and 28 (n = 12) days after transplantation and beta cell replication, apoptosis and mass were determined.

RESULTS:

500 islets is an insufficient mass to restore normoglycemia and therefore, all animals but one (IL-1Ra group) remained hyperglycemic until the end of the study. Beta cell replication (determined by BrdU incorporation) was significantly increased in Ad-IL-1Ra group on days 3 (0.78 ± 0.23%), 10 (1.15 ± 0.16%) and 28 (1.22 ± 0.2%) after islet transplantation compared to beta cell replication in normal pancreas (0.24 ± 0.04%; p< 0.05). In contrast, in control group, beta cell replication was not increased on day 3 after transplantation (0.41 ± 0.11%), and although it increased on day 10 (0.89 ± 0.18%; p< 0.01) it was reduced again on day 28 (0.59 ± 0.10%) in agreement with previous reports of limited beta cell replication with persistent hyperglycemia. Beta cell apoptosis (determined by TUNEL method) was significantly increased in transplanted islets from both groups compared to pancreas. Although Ad-IL-1Ra group showed lower beta cell apoptotic levels than control group, differences did not reach statistical significance. The initially transplanted â-cell mass (1.34 ± 0.03 mg) was similarly reduced in both control (0.32 ± 0.06 mg) and Ad-IL-1Ra groups (0.45 ± 0.10 mg) (p<0.001) on day 3 after transplantation. In Ad-IL-1Ra islet grafts, beta cell mass increased after 10 (1.04 ± 0.091 mg; p< 0.010) and 28 (0.8 ± 0.24 mg) days of transplantation. In contrast, beta cell mass of control group was also increased on day 10 after transplantation (0.69 ± 0.12 mg), but it dropped again on day 28 (0.41 ± 0.05 mg) paralleling with the evolution of beta cell replication in this group.

CONCLUSIONS:

Islets overexpressing IL-1Ra showed an increased beta cell replication and a preserved beta cell mass after transplantation, that was maintained even after longterm exposure to hyperglycemia.

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Whitmire, Rachel Elisabeth. "Self-assembling polymeric nanoparticles for enhanced intra-articular anti-inflammatory protein delivery." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/43587.

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The goal of this thesis was to develop a new drug-delivering material to deliver anti-inflammatory protein for treating OA. Our central hypothesis for this work is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint. The primary goal of this work was to synthesize a block copolymer that could self-assemble into injectable, sub-micron-scale particles and would allow an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and cyclohexyl methacrylate, a hydrophobic monomer, for particle stability. We engineered the copolymer and tested it in both in vitro culture experiments and an in vivo model to evaluate protein retention in the knee joint. The rationale for this project was that the rational design and synthesis of a new drug- and protein-delivering material can create a modular polymer particle that can deliver multi-faceted therapies to treat OA. This work characterizes the in vitro and in vivo behavior of our polymer particle system. The protein tethering strategy allows IL-1ra protein to be tethered to the surface of these particles. Once tethered, IL-1ra maintains its bioactivity and actively targets synoviocytes, cells crucial to the OA pathology. This binding happens in an IL-1-dependent manner. Furthermore, IL-1ra-tethered particles are able to inhibit IL-1beta-induced NF-kappaB activation. These studies show that this particle system has the potential to deliver IL-1ra to arthritic joints and that it has potential for localizing/targeting drugs to inflammatory cells of interest as a new way to target OA drug treatments.

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Khan, Shamila. "Therapeutic effect of Interleukin-4 and Interleukin-1 Receptor Antagonist in Actinobacillus pleuropneumoniae challenged pigs." Thesis, The University of Sydney, 2005. http://hdl.handle.net/2123/625.

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Immunological stressors, in the form of clinical and sub-clinical disease are currently controlled using both prophylactic antibiotics in-feed, and therapeutic antibiotic treatment. Respiratory disease, primarily Actinobacillus pleuropneumoniae (App) infection, is recognised as a major factor causing reduced productivity in pigs. This thesis reports investigations into the use of novel immunomodulators in particular Interleukin 4 (IL-4) and Interleukin 1 receptor antagonist (IL-1ra) as alternatives to antibiotics to treat App infection. Immunological and molecular biological assays were used to investigate and accumulate data. An in vitro study undertaken to find potential anti-inflammatory substances, revealed that Interleukin 8 (IL-8) mRNA production stimulated by PMA or LPS in whole pigs' blood was suppressed by IL-4. IL-1ra also suppressed stimulated IL-8 mRNA production by heat killed App bacteria (KB) in vitro. An acute LPS challenge in pigs in vivo however, showed no variation in illness or weight loss between pigs treated prophylactically with anti-inflammatory substance (IL-4 and IL-1ra) and saline treated pigs. The use of plasmids as a delivery system for anti-inflammatory substance did not show promise since it did not enhance growth or prolong the expression of the substances in the pigs. However, in the chronic App challenge model IL-4 and IL-1ra administered prophylactically in vivo showed an ability to improve growth. The therapeutic administration of IL-4 and IL-1ra to App challenged pigs showed no difference in pigs' growth, regardless of the treatment or control administered. To conclude, IL-4 and IL-1ra showed promise when administered prophylactically and improved growth and abrogated disease under conditions of App challenge. However when IL-4 and IL-1ra where administered therapeutically they did not perform as well. Moreover these compounds have potential as a commercial application to reduce the growth reduction caused by disease such as App.

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Books on the topic "IL-1ra"

Bresnihan, Barry, and Jean-Michel Dayer. IL-1Ra in the Treatment of Rheumatoid Arthritis. Taylor & Francis Group, 2004.

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Dayer, Jean-Michel. Il-1ra in the Treatment of Rheumatoid Arthritis. Taylor & Francis Group, 2001.

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Il-1Ra in the Treatment of Rheumatoid Arthritis. Routledge, 2003.

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Bresnihan, Barry, and Jean-Michel Dayer. IL-1ra in the Treatment of Rheumatoid Arthritis: Pocket Book. Informa Healthcare, 2001.

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Book chapters on the topic "IL-1ra"

Opal, S. M. "IL-1ra as a Therapeutic Modality in Sepsis." In Yearbook of Intensive Care and Emergency Medicine 1993, 107–13. Berlin, Heidelberg: Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-84904-6_10.

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Xie, Bo. "One of the TNF Superfamily Members: Bifunctional Protein, TNFR2-Fc-IL-1ra." In Methods in Molecular Biology, 215–22. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0669-7_18.

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Dhainaut, J. F., J. P. Mira, and F. Brunet. "Investigational Therapy of Sepsis: Anti-TNF, IL-1ra, Anti-PAF and G-CSF." In Update in Intensive Care and Emergency Medicine, 267–82. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79224-3_17.

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Rau, R. "Beeinflussung der radiologischen Progression der rheumatoiden Arthritis durch Behandlung mit einem rekombinanten humanen IL-1-Rezeptor-Antagonisten (IL-1ra)." In Der IL-1-Rezeptor-Antagonist im Zytokin-Netzwerk, 51–69. Heidelberg: Steinkopff, 2002. http://dx.doi.org/10.1007/978-3-642-53780-6_6.

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Bonaccio, M., W. Ertel, J. Fandino, J. Kennedy, R. Stocker, and O. Trentz. "Die Bedeutung des Interleukin-1 Rezeptor Antagonisten (IL-1ra) für die Interleukin-1β (IL-1β) induzierte systemische Inflammation bei Patienten mit ausgedehnten Mehrfachverletzungen." In Chirurgisches Forum ’94, 535–38. Berlin, Heidelberg: Springer Berlin Heidelberg, 1994. http://dx.doi.org/10.1007/978-3-642-78905-2_106.

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"IL-1Ra." In Encyclopedia of Medical Immunology, 375. New York, NY: Springer New York, 2020. http://dx.doi.org/10.1007/978-1-4614-8678-7_300184.

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Mak, Tak W., Josef Penninger, John Roder, Janet Rossant, and Mary Saunders. "IL-1ra." In The Gene Knockout FactsBook, 585–86. Elsevier, 1998. http://dx.doi.org/10.1016/b978-012466044-1/50327-6.

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"IL-1RA." In Dictionary of Rheumatology, 90. Vienna: Springer Vienna, 2009. http://dx.doi.org/10.1007/978-3-211-79280-3_499.

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"Interleukin-1 Receptor Antagonist Protein (IL-1Ra)." In Spinal Injection Techniques, edited by Theodoros Theodoridis and Juergen Kraemer. Stuttgart: Georg Thieme Verlag, 2009. http://dx.doi.org/10.1055/b-0034-66327.

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Jacques, Claire, Marjolaine Gosset, Francis Berenbaum, and Cem Gabay. "The Role of IL‐1 and IL‐1Ra in Joint Inflammation and Cartilage Degradation." In Interleukins, 371–403. Elsevier, 2006. http://dx.doi.org/10.1016/s0083-6729(06)74016-x.

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Conference papers on the topic "IL-1ra"

Gorth, Deborah J., John T. Martin, George R. Dodge, Nader M. Hebela, Neil R. Malhotra, Robert L. Mauck, Dawn M. Elliott, and Lachlan J. Smith. "In Vivo Delivery of IL-1ra From PLGA Microspheres Prevents IL-1β Induced Glycosaminoglycan Loss in the Rat Caudal Intervertebral Disc." In ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/nemb2013-93134.

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Inflammation plays a central role in the progression of disc degeneration, which is strongly implicated as a cause of low back pain. The objectives of this in vivo study were: first to investigate whether PLGA microspheres could be retained in the disc, and second to test whether IL-1ra delivered from those microspheres could effectively inhibit IL-1β induced extracellular matrix loss using a rat caudal disc model. Three caudal disc levels (C6–7 to C8–9) of 6 Sprague-Dawley rats were exposed via a dorsal midline incision for treatment. Fluorescently labeled microspheres were clearly visible in the disc at all time points except 8 weeks. The GAG content of discs injected with IL-1β alone was significantly lower than that of the intact controls and the microsphere treatment group. For discs injected with both IL-1β and IL-1ra microspheres, GAG content was not different from the intact control. In this study we demonstrated for the first time that IL-1ra delivered from microspheres prevents IL-1β induced GAG loss in vivo, and that microspheres are retained in the disc space for at least 4 weeks.

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Fenner, H., S. Zueger, and M. Schattenkirchner. "THU0212 Imbalance between synovial il-1 activity/il-1ra production and disease course in rheumatoid arthritis." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.1114.

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Kay, J., S. Bryant, MW Cravets, and D. McCabe. "FRI0002 Il-1 receptor antagonist (il-1ra) treatment is associated with improvement of anaemia in rheumatoid arthritis." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.1131.

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Chen, C. T., S. Park, M. Bhargava, and P. A. Torzilli. "Inhibitory Effect of Mechanical Load on IL-1 Induced Cartilage Degradation Is Mediated by Interferon-Gamma and IL-1 Receptor 1." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-193230.

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Matrix remodeling in articular cartilage is regulated by the elevation and activation of aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases (MMPs) [2–4, 7–9, 10]. Several recent studies from our and other groups have shown that mechanical loading can counteract interleukin 1 (IL-1) induced pro-inflammatory and catabolic events by down-regulating aggrecanases, MMPs, and pro-inflammatory genes [1, 3, 5, 6], but the molecular mechanism is not clear. Many previous studies have shown that the regulation of pro-inflammatory effect of IL-1 come from several aspects: anti-inflammatory cytokines (TGF-β, IL-10, IL-6 and interferon γ), IL-1 receptor related proteins (IL-1R1, IL-1R2, and IL-1Ra) as well as a family of intracellular inhibitory protein called Suppressor Of Cytokine Signaling (SOCS.) SOCS1 and SOCS3 are especially important, since they can inhibit both MAPK and NF-κB pathways induced by IL-1 [12]. The objective of this study was to determine whether mechanical load affected anti-inflammatory mediators along with anti-catabolic events.

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Miller, DM, E. Ng, MH Schiff, SB Cohen, and B. Bresnihan. "FRI0077 Durability and rapidity of response for rheumatoid arthritis patients receiving therapy with anakinra (il-1ra)." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.1206.

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Qin, Yong, Suhendan Ekmekcioglu, Nancy Poindexter, Julie Ellerhorst, and Elizabeth A. Grimm. "Abstract 4506: Elevated expression of IL-1 induces iNOS/NO production and inhibits IL-1Ra synthesis leading to progression of metastatic melanoma." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4506.

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Wang, Wei, Yan Liu, Jian Guo, Huiwen He, Junling Xie, Chong Chen, and Yunping Luo. "Abstract 724: MicroRNA-100/mTOR/IL-1ra signaling maintains TAMs phenotype and enhances tumor cell stemness property in mouse breast cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-724.

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Atkinson, JE, RV House, PS Cranmer, AE Colucil, H. Davis, CK Edwards, and DM Miller. "THU0096 Effect of anakinra (il-1ra) and soluble tumour necrosis factor receptor i (stnf-ri) on cellular immune function in rats." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.973.

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Feige, U., YL Hu, S. Morony, G. Campagnuolo, D. Duryea, and B. Bolon. "OP0016 Osteoclast numbers in joints of rats with adjuvant arthritis are decreased by treatment with il-1ra and/or peg stnf-ri." In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.1025.

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Dabrosin, C., G. Lindahl, A. Abrahamsson, and N. Saarinen. "Abstract P1-02-06: Tamoxifen, Flaxseed and the Lignan Enterolactone Increase Stroma and Cancer Cell Derived IL-1Ra, Decrease Tumor Growth and Angiogenesis in Estrogen Dependent Breast Cancer Explants." In Abstracts: Thirty-Third Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 8‐12, 2010; San Antonio, TX. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/0008-5472.sabcs10-p1-02-06.

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Academic literature on the topic 'IL-1ra'

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