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Shepherd, Joanna. "Inflammatory diseases in mice lacking interleukin-1 receptor antagonist." Thesis, University of Sheffield, 2003. http://etheses.whiterose.ac.uk/14727/.
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Greenhalgh, Andrew. "Actions of interleukin-1 receptor antagonist in cerebral ischaemia." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/actions-of-interleukin1-receptor-antagonist-in-cerebral-ischaemia(50aacd97-68c1-4f91-90b5-8f8deff5d21d).html.
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Cerebral ischaemia, or stroke, is a leading cause of death and disability worldwide. Ischaemic stroke, as a result of arterial occlusion, and subarachnoid haemorrhage (SAH), as a consequence of arterial rupture in the subarachnoid space, are major subtypes of stroke. Treatment options for both are limited, and many therapeutic strategies have failed. In ischaemic stroke, lack of evidence of brain penetration of treatments has been cited as a major weakness and contributing factor to failed clinical trials. In SAH, animal models do not always mimic key pathophysiological hallmarks of the disease, hindering development of new therapeutics. Inflammation is strongly associated with brain injury after cerebral ischaemia and inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1) represents apossible therapeutic target. Therefore, the key objectives of this thesis were; (1) to improve preclinical data on a promising stroke treatment, interleukin-1 receptor antagonist (IL-1Ra), by investigating its pharmacokinetic profile and brain penetration in a rat model of ischaemic stroke, (2) to investigate the endovascular perforation model of SAH in rat, as a tool for the investigation of neuroprotectants, and (3) to examine the role of the inflammatory response in the SAH model and the effects of IL-1Ra. The neuroprotective effect, pharmacokinetic profile and brain penetration of IL-1Ra were assessed after a single subcutaneous (s.c.) dose (100mg/kg) in rats, after transient (90 min) middle cerebral artery occlusion (MCAo). A single s.c. dose of IL-1Ra reduced neuronal damage, resulted in sustained, high concentrations of IL-1Ra in plasma and cerebrospinal fluid and also penetrated brain tissue exclusively in areas of blood brain-barrier (BBB) breakdown. An endovascular perforation model of SAH in rat was investigated and produced widespread multifocal infarcts. In this model, administration of IL-1Ra (s.c.) reduced BBB breakdown, which correlated with injury at 48 h. IL-1_ was expressed in the brain early after SAH in areas associated with haem oxygenase-1 (HO-1) expression, indicating the presence of free haem. Stimulation of primary mouse mixed glial cells in vitro with haem induced expression and release of IL-1 alpha but not IL-1 beta. These data, after MCAo in rat, are the first to show that a single s.c. dose of IL-1Ra rapidly reaches salvageable brain tissue and is neuroprotective. This allows confidence that IL-1Ra is able to confer its protective actions both peripherally and centrally. After experimental SAH, we suggest that haem, a breakdown product of haemoglobin, released from lysed red blood cells in the subarachnoid space, acts as a danger associated molecular pattern (DAMP) driving IL-1- dependent inflammation. These data provide new insights into inflammation after SAH-induced brain injury and suggest IL-1Ra as a candidate treatment for the disease. Overall, these findings strengthen preclinical data supporting IL-1Ra as a neuroprotective therapy for ischaemic stroke, and identify SAH as a new indication for treatment with IL-1Ra.
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Tarlow, Joanna Karen. "Interleukin-1 receptor antagonist gene polymorphism in chronic inflammatory diseases." Thesis, University of Sheffield, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296761.
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Galea, James. "Pharmacokinetics of intravenous interleukin-1 receptor antagonist in subarachnoid haemorrhage." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509780.
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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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La, Eunhye. "The regulation of the interleukin 1 receptor antagonist in mouse skin carcinogenesis /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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Cantrill, Carina. "Interactions of interleukin-1 receptor antagonist with primary porcine brain endothelial cells." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509889.
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Khan, Shamila. "Therapeutic effect of Interlenkin-4 and Interleukin-1 receptor antagonist in Actinobacillus pleuropneumoniae challenged pigs." University of Sydney. Anatomy and Pathology, 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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Fischer, Philipp. "Inhibition of inflammatory vasculopathic processes by interleukin-1 receptor antagonist - transduced endothelial progenitor cells." kostenfrei, 2008. http://mediatum2.ub.tum.de/node?id=669329.
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Ashawesh, Mohamed. "Ultrasound enhanced gene delivery of secreted Interleukin 1 receptor antagonist in a murine vascular injury model." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/18481/.
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Ultrasound (US) mediated gene delivery (UMGD) is a non-viral technique for gene transfer that has been a developing technology over the past 18 years. Non-viral UMGD as an approach is safe, relatively cheap and can be tolerated even over multiple exposures. US exposure has previously been demonstrated to increase DNA transfer and expression in endothelial cells (EC) and vascular smooth muscle cells (VSMC) in vitro and ex vivo in a saphenous vein graft model. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that plays a key role in cardiovascular diseases and vascular injury. Treatment with the endogenous inhibitor interleukin-1 receptor antagonist (IL-1Ra) is an effective treatment in animal models of vascular disease and some inflammatory clinical conditions. However, Anakinra (the clinically approved formulation of IL-1Ra) must be given as daily subcutaneous (SC) injections (due to a short t ½), which is inconvenient (high burden for compliance) and very expensive. In this project I have tested US parameters for ‘best’ gene expression in the mouse hind limb, demonstrated long-term expression utilising a repeat dosing regime and finally investigated the therapeutic efficacy of intramuscular (IM) UMGD of pCMV6-SIL1Ra in a rodent arterial injury model compared with continuous delivery of Anakinra via osmotic mini-pump. Following experiments to determine the US dose, duration of expression and therefore treatment schedule, I have demonstrated that this new UMGD technique of pCMV6-SIL1Ra, every 4 days over a period of 28 days significantly decreased neointima/media (N/M) ratio in a murine vascular injury model. Furthermore, there was no significant difference between mice treated with pCMV6-SIL1Ra-UMGD and those receiving continuous Anakinra infusion by osmotic mini-pump (25 mg/kg/), suggesting that UMGD was at least as efficacious as drug treatment in reducing neointima formation. The role of IL-1 in neointima formation following vascular injury is not new but these novel data demonstrate the potential for UMGD to achieve therapeutic levels of gene/protein expression in an animal model and highlight the potential for further development. This technique of UMGD utilising a secreted protein and easily accessible muscle tissue from which to express it warrants further investigation as a possible treatment for other cardiovascular and systemic/peripheral diseases where a secreted protein is an attractive drug treatment.
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Rütten, Simon, Gerald F. Schusser, Getu Abraham, and Wieland Schrödl. "Release kinetics of tumor necrosis factor-α and interleukin-1 receptor antagonist in the equine whole blood." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-205268.
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Background: Horses are much predisposed and susceptible to excessive and acute inflammatory responses that cause the recruitment and stimulation of polymorphnuclear granulocytes (PMN) together with peripheral blood mononuclear cells (PBMC) and the release of cytokines. The aim of the study is to develop easy, quick, cheap and reproducible methods for measuring tumor necrosis factor alpha (TNF-α) and interleukin-1 receptor antagonist (IL-1Ra) in the equine whole blood cultures ex-vivo time- and concentration dependently. Results: Horse whole blood diluted to 10, 20 and 50 % was stimulated with lipopolysaccharide (LPS), PCPwL (a combination of phytohemagglutinin E, concanavalin A and pokeweed mitogen) or equine recombinant TNF-α (erTNF-α). TNF-α and IL-1Ra were analyzed in culture supernatants, which were collected at different time points using specific enzyme-linked immunosorbent assays (ELISA). Both cytokines could be detected optimal in stimulated 20 % whole blood cultures. TNF-α and IL-1Ra releases were time-dependent but the kinetic was different between them. PCPwL-induced TNF-α and IL-1Ra release was enhanced continuously over 24–48 h, respectively. Similarly, LPS-stimulated TNF-α was at maximum at time points between 8–12 h and started to decrease thereafter, whereas IL-1Ra peaked later between 12–24 h and rather continued to accumulate over 48 h. The equine recombinant TNF-α could induce also the IL-1Ra release. Conclusions: Our results demonstrate that similar to PCPwL, LPS stimulated TNF-α and IL-1Ra production time-dependently in whole blood cultures, suggesting the suitability of whole blood cultures to assess the release of a variety of cytokines in health and diseases of horse.
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Mathew, Daniel J. Lucy Matthew C. Geisert Rodney D. "Effect of RU486, a progesterone antagonist, on uterine progesterone receptor, embryonic development and ovarian function during early pregnancy in pigs." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/5371.
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The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on December 29, 2009). Thesis advisor: Dr. Matthew C. Lucy and Rodney D. Geisert. Vita. Includes bibliographical references.
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Venteclef, Nicolas. "Etude du rôle << Liver Receptor Homolog-1 >> dans la régulation de la réponse inflammatoire hépatique et dans l'homéostasie du cholestérol." Paris 6, 2007. http://www.theses.fr/2007PA066268.
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Etude du rôle de « Liver Receptor Homolog-1 » (LRH-1 ; NR5A2) dans la régulation de la réponse inflammatoire hépatique et dans l’homéostasie du cholestérol Les récepteurs nucléaires sont des facteurs de transcription impliqués dans des processus biologiques cruciaux tels que la reproduction, le développement et la différenciation. Le « liver receptor homolog-1 » (LRH-1 ; NR5A2) est un facteur de transcription, constitutivement actif, appartenant à la famille des récepteurs nucléaires. Il est essentiellement exprimé dans les tissus d’origine endodermique tels que le foie, le pancréas et l’intestin. LRH-1 joue un rôle majeur dans le développement, la stéroïdogénèse et l’homéostasie du cholestérol via la régulation du transport réverse du cholestérol et la biosynthèse des acides biliaires. Récemment, nous avons démontré le rôle de LRH-1 dans la régulation de la réponse de phase aiguë au niveau hépatique. En effet, la sur-expression de LRH-1dans des hépatocytes résulte en l’inhibition de l’induction de l’expression d’haptoglobine et SAA par les cytokine IL1 et IL6. De plus, l’induction de la réponse inflammatoire est significativement exacerbée dans des cellules hépatiques déficientes pour LRH-1. Des études de promoteur, d’ARN interférence et de chromatine immuno-précipitation révèlent que LRH-1 régule la réponse inflammatoire d’une part en antagonisant la voie de signalisation C/EBP et d’autre part en induisant l’expression de IL-1RA (« Interleukin-1 Receptor Antagonist »). L’activité anti-inflammatoire de LRH-1 est démontrée in vivo dans les souris hétérozygote pour LRH-1. LRH-1 est décrit comme régulateur du métabolisme lipidique en contrôlant l’expression des gènes impliqués dans la régulation de la synthèse des acides biliaires et dans l’homéostasie du cholestérol. Les particules HDL sont considérées comme des particules anti-anthérogène par leur capacité à promouvoir le transport réverse du cholestérol. Des études récentes rapporte que ApoM semble important dans la formation des particules prè-HDL et dans l’efflux cholestérol induit par les particules HDL. Par ailleurs, ApoM inhibe la progression de l’athérosclérose dans les souris LDLr KO. Nous avons étudié le rôle de LRH-1 dans la régulation du gène codant ApoM. En utilisant des hépatocytes déficient pour LRH-1 ou sur exprimant LRH-1, nous avons démontré que LRH-1 régule l’expression de ApoM en se liant à un LRH-1 RE localisé dans le promoteur du gène. Nous démontrons également que le répresseur transcriptionnelle SHP inhibe l’expression de ApoM en inhibant l’activité transcriptionnelle de LRH-1 in vitro et in vivo. Les propriétés anti-inflammatoires de LRH-1 et son rôle dans l’homéostasie du cholestérol sont confirmés par la caractérisation des souris LRH-1 conditionnelles KO. L’ensemble de ces résultats démontre que LRH-1 est un régulateur physiologique de la réponse de phase aiguë et joue un rôle majeur dans le métabolisme du HDL-cholestèrol.
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Mentro, Anne M. "Vitamin A status and inflammation during the first week of life in extremely premature infants at risk for bronchopulmonary dysplasia." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1092500146.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xiv, 133 p.; also includes graphics (some col.) Includes bibliographical references (p. 107-133). Available online via OhioLINK's ETD Center
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Lasarzik, Juliane [Verfasser]. "Interleukin-1 receptor antagonist and interleukin-1 beta levels in equine synovial fluid of normal and osteoarthritic joints and the influence of two different autolougous conditioned serum treatment intervals on cytokine and cartilage biomarker levels in equine osteoarthritic joints / Juliane Lasarzik." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1137206624/34.
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Wojitani, Maria Dulce Caoro Horie. "Avaliação da frequência do polimorfismo nos genes que codificam a lecitina ligadora da manose (MBL) e o antagonista do receptor da interleucina-1 (IL1-Ra) em mulheres portadoras de candidíase vulvovaginal recorrente." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-23082011-135628/.
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A candidíase vulvovaginal corresponde a uma das mais frequentes infecções do trato reprodutivo. Estima-se que 75% das mulheres na idade reprodutiva experimentarão pelo menos um episódio de candidíase vulvovaginal durante suas vidas, a maioria evoluirá com episódios infrequentes, entretanto, 5% sofrerão recorrência, ou seja, quatro ou mais episódios de candidíase vulvovaginal comprovadas clínica e laboratorialmente no período de 1ano. Os mecanismos pelos quais as recorrências ocorrem ainda são pouco conhecidos, estando provavelmente relacionados à alterações na imunidade local. O presente estudo teve como objetivo avaliar as associações entre os polimorfismos nos genes que codificam a lecitina ligadora de manose (MBL) e do antagonista do receptor da interleucina 1 (IL1-Ra) com a candidíase vulvovaginal recorrente (CVVR) em mulheres brasileiras. Foram estudadas 100 mulheres portadoras de CVVR atendidas no Serviço de Imunologia Genética e Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. Para a análise dos polimorfismos nos genes que codificam para a MBL e o IL1-Ra realizou-se coleta de células bucais que foram enviadas para Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University Resultados: Mulheres com candidíase vulvovaginal recorrente apresentaram maior frequência de polimorfismo no códon 54 do gene que codifica a MBL quando comparadas a mulheres saudáveis. Não foram observadas diferenças estatisticamente significativas na frequência do polimorfismo do gene que codifica o IL1-Ra entre os grupos estudadosVulvovaginal candidiasis is the most common genital infection in women during their childbearing years. About 75% of women suffer at least one syntomatic episode during their lives. Most of them will have infrequent episodes, but 5% will suffer recurrent episode of vulvovaginal candidiasis. The mechanisms responsible for recurrent vulvovaginal candidiasis (RVCC) remain a matter of speculation, although an alteration in local immunity appears to be a major factor. The aim of this study was to assess the correlation between polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL1-Ra) and RVCC in women from São Paulo, Brazil. The study population consisted of 100 women with RVCC, who were seen at Serviço de Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. To analyse for the MBL códon 54 gene polymorphism and for IL1-Ra, buccal cells were obtained with a cotton swabs and shipped to New York at ambient temperature. The polymorphisms were identified in the Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University. Results: Women with RVVC present a high frequency of polymorphisms at codon 54 in the gene coding for MBL; on the other hand there were no differences in polymorphism frequency in the gene coding for IL1-Ra when compared to control women
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Cianciarullo, Marco Antonio. "Estudo da homeostase dos mediadores pró-inflamatórios e antiinflamatórios na sepse neonatal." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-22082008-155547/.
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Objetivos: Avaliar a utilidade dos mediadores pró-inflamatórios (TNF-alfa, IL-1 beta e IL-6), dos mediadores antiinflamatórios (IL-10 e IL-1Ra) e da Proteína C reativa (PCR) para o diagnóstico na sepse neonatal; verificar se os valores séricos isolados ou a relação entre IL-6 e IL-1Ra têm valor preditivo de gravidade, na evolução clínica da doença; determinar se a homeostase entre os mediadores pró-inflamatórios e antiinflamatórios e a PCR definem o prognóstico da doença. Casuística e métodos: Foram incluídos no estudo 31 recém-nascidos (RN) internados na UCINE ou no Hospital Universitário com diagnóstico de sepse, baseado em critérios clínicos e laboratoriais. Os RN com diagnóstico de sepse foram subdivididos em dois grupos de acordo com a evolução clínica: grupo sepse: os que tiveram boa evolução e grupo sepse grave, os que tiveram evolução complicada por choque séptico e/ou CIVD e/ou FMOS e/ou óbito. Além dos exames de rotina para sepse, forma mensurados nos dias 0, 3 e 7 de evolução a partir do diagnóstico, os níveis séricos de TNF-alfa, IL-1 beta, IL-6, IL-10 e IL-1Ra. Resultados: Na análise evolutiva geral, todos os mediadores inflamatórios apresentaram mensuração elevada no dia do diagnóstico (dia 0), com decréscimo dos valores no decorrer do tempo. Entre os mediadores pró-inflamatórios, a TNF-alfa, a IL-6 e a IL-1 beta se mostraram adequados para o diagnóstico, no entanto para o seguimento, a melhor foi a IL-6. Entre os mediadores antiinflamatórios a IL-10 seguiu os padrões dos mediadores próinflamatórios acompanhando a resolução do processo séptico, enquanto a IL-1Ra apresentou decréscimos até o 3º dia e permaneceu estável até o 7º dia caracterizando a perpetuação da ação antiinflamatória desta citocina. Quanto às relações entre mediadores pró-inflamatórios e antiinflamatórios (relação IL-6/IL-1Ra e IL-6/(IL-6 + IL-1Ra) observamos que a IL-6/IL-1Ra apresentou relação com a evolução do processo séptico, mostrando inicialmente predomínio da ação próinflamatória no dia 0 e antiinflamatória no dia 7. A PCR acompanhou de forma muito semelhante as curvas da TNF-alfa, L-6 e IL-10. Quando se subdividiu a casuística em grupos, sepse e sepse grave, observamos que os RN com sepse com boa evolução apresentaram níveis séricos médios de TNF-alfa, IL-1 beta e IL-10 próximos aos níveis mínimos detectáveis e estas citocinas nos RN com sepse grave.Objectives - To evaluate the utility of the pro-inflammatory mediators (TNF-alfa, IL1-beta, and IL-6), the anti-inflammatory mediators (IL-10 and IL-1Ra) and C-Reactive Protein (CRP) for the diagnosis of neonatal sepsis; to verify whether the isolated seric values or the relation between IL-6 and IL-1Ra have predictive values for severity regarding the clinical outcome, and to ascertain if the homeostasis between the pro-inflammatory and anti-inflammatory mediators and CPR can define the prognosis of the disease. Patients and Methods - The study included 31 newborns (NB) admitted to the UCINE (External Neonatal Unit) or to Hospital Universitário (São Paulo University Hospital) with diagnosis of sepsis based upon clinical and laboratorial parameters. The NB with diagnosis of sepsis were further subdivided into 2 groups according to the clinical outcome: sepsis group: containing those NB who evolved to a positive outcome, and severe sepsis group, in turn composed of the NB with unsatisfactory outcomes due to complications caused by septic shock and/or DIVC and/or FMOS and/or death. On days 0, 3, and 7 following diagnosis the seric levels of TNF-alfa, IL-1 beta, IL-6, IL-10, and IL-1Ra were measured in addition to the routine sepsis workup. Results - The general follow-up analysis revealed that all the inflammatory mediators presented elevated levels at diagnosis (day 0) with a decrease of these values over time. Regarding the pro-inflammatory mediators, TNF-alfa, IL-6 and IL-1 beta were satisfactory for diagnosis, whereas IL-6 was more accurate for follow-up. In relation to the anti-inflammatory mediators, IL-10 revealed the same pattern of the pro-inflammatory mediators following the septic process resolution, whereas IL-1Ra gradually decreased until the 3rd day but hence remained stable until the 7th day, thus characterizing the continuity of the anti-inflammatory action of this cytokine. Concerning the inter-relation between the pro and anti-inflammatory mediators (IL-6/IL-1Ra relation and IL-6/(IL6+IL-1Ra)) we observed that the IL-6/IL-1Ra correlated with the septic process evolution with predominance of the proinflammatory action on day 0 and of the anti-inflammatory action on day 7. The CRP levels, we observed that in the sepsis group with satisfactory outcome on day 0 the seric values were higher than in the severe sepsis group, although on days 3 and 7 these values decreased more substantially, while in the sepsis group they increased on day 3 followed by a gradual decrease until day 7. Conclusions - The analyzed mediators were effective in the diagnosis of neonatal sepsis and also predictive of the degree of severity, mainly with regards to cytokines IL-6 and IL-1Ra. The homeostatic equilibrium/disequilibrium was correlated to the type of disease outcome: sepsis with no complications versus severe sepsis.
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Schizas, Nikos. "Neuroprotection in the Injured Spinal Cord : Novel Strategies using Immunomodulation, Stem cell Transplantation and Hyaluronic acid Hydrogel carriers." Doctoral thesis, Uppsala universitet, Ortopedi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-251477.
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The overall aim of this thesis was to establish strategies to minimize secondary damage to the injured spinal cord. Secondary damage that follows spinal cord injury (SCI) involves inflammatory and excitotoxic pathways. Regulation of these pathways using immunomodulatory and neuroprotective substances potentially protects the injured spinal cord from further damage. We also developed and studied resorbable biomaterials to be used as carriers for potential neuroprotectants to the injured spinal cord. We used transversal spinal cord slice cultures (SCSCs) derived from postnatal mice as a model. SCSCs were maintained on different biomaterials and were studied after treatment with immunomodulatory and/or neurotrophic factors. They were further excitotoxically injured and subsequently treated with interleukin-1 receptor antagonist (IL1RA) or by neural crest stem cell (NCSC)-transplantation. The results show that biocompatible and resorbable hydrogels based on hyaluronic acid (HA) preserved neurons in SCSCs to a much higher extent than a conventional collagen-based biomaterial or standard polyethylene terephthalate (PET) membrane inserts. Glial activation was limited in the cultures maintained on HA-based hydrogel. The anti-inflammatory factor IL1RA protected SCSCs from degenerative mechanisms that occur during in vitro incubation, and IL1RA also protected SCSCs from excitotoxic injury induced by N-Methyl-d-Aspartate (NMDA). IL1RA specifically protected neurons that resided in the ventral horn, while other neuronal populations such as dorsal horn neurons and Renshaw cells did not respond to treatment. Finally, transplantation of NCSCs onto excitotoxically injured SCSCs protected from neuronal loss, apoptosis and glial activation, while NCSCs remained undifferentiated. The results presented in this thesis indicate that carriers based on HA seem to be more suitable than conventional collagen-based biomaterials since they enhance neuronal survival per se. The observed neuroprotection is likely due to biomechanical properties of HA. IL1RA protects SCSCs from spontaneous degeneration and from NMDA-induced injury, suggesting that excitotoxic mechanisms can be modulated through anti-inflammatory pathways. Different neuronal populations are affected by IL1RA to various degrees, suggesting that a combination of different neuroprotectants should be used in treatment strategies after SCI. Finally, NCSCs seem to protect SCSCs from excitotoxic injury through paracrine actions, since they remain undifferentiated and do not migrate into the tissue during in vitro incubation. It seems that combinations of neuroprotectants and carrier substances should be considered rather than one single strategy when designing future treatments for SCI. Incorporation of neuroprotectants such as IL1RA combined with stem cells in injectable biocompatible carriers based on HA is the final goal of our group in the treatment of SCI.
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Thapa, Pariksha. "Kinetics of Microvesicle Particle Release in Keratinocytes." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1566504910360327.
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Thirumangalathu, Renuka. "Understanding physical and chemical stability of proteins in solution : relevance to therapeutic protein and monoclonal antibody formulations /." Connect to abstract via ProQuest. Full text is not available online, 2007.
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Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 133-143). Online version available via ProQuest Digital Dissertations.
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Gillespie, Shannon L. "Pathways to Shortened Gestation among African American Women." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1448896905.
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HAMZAOUI, NADIM. "Interet de l'etude des concentrations plasmatiques de l'interleukine 6, du recepteur soluble de l'interleukine 6, et de l'antagoniste de l'interleukine 1, dans la maladie de crohn : a propos de 94 observations." Lyon 1, 1994. http://www.theses.fr/1994LYO1M257.
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Perrier, Stéphane. "L'interleukine-1 recepteur antagoniste (il1 ra) : caracterisation dans la muqueuse buccale et etude physiopathologique dans le syndrome de gougerot-sjogren (doctorat : immunologie clinique)." Clermont-Ferrand 1, 1999. http://www.theses.fr/1999CLF1MM12.
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廖健翔. "Interleukin-1 receptor antagonist-based immunotherapy on autoimmune diabetes." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/03410938336018266922.
Full textAbstract:
碩士國防醫學院
微生物及免疫學研究所
88
Insulin-dependent diabetes mellitus (IDDM) is caused by a progressive autoimmune destruction of the insulin-producing b cells in the pancreatic islets of Langerhans. Both genetic predisposition and environmental factors contribute to its pathogenesis. A widely used animal model for dissecting immunopathological mechanisms in IDDM and for developing preventive and/or therapeutic strategies is the non-obese diabetic (NOD) mouse, an inbred strain that spontaneously develops an autoimmune diabetes resembling human IDDM. Interleukin-1b (IL-1b), a potent pro-inflammatory cytokine, has been shown to mediate the autoimmune diabetic process and to trigger the destruction of b cells in several animal models. Blocking the IL-1b bioactivity by IL-1 receptor antagonist (IL-1ra) or monoclonal anti-IL-1b has been reported by our laboratory to inhibit the disease process on the delay onset of diabetes or the decrease of disease frequency. Since naked nucleic acid vectors carrying cytokine genes are potentially useful candidates for the prevention/treatment of autoimmune diseases, we seek to treat/prevent autoimmune diabetes by injecting IL-1ra-expressing vectors. Our results show a significant protection from cyclophosphamide-induced diabetes in NOD mice intramuscularly or intravenously injected with pcDNA-IL-1ra vector. We also observed a slight decrease of delayed-type hypersensitivity reaction and a moderate inhibition of host defense against bacterial infection in those IL-1ra-treated mice. Despite these potential side-effects, IL-1ra DNA therapy could be very useful for autoimmune diabetes.
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Choi, Sooshin. "Interleukin-1 receptor antagonist as a novel therapeutic target for obesity." Master's thesis, 2014. http://hdl.handle.net/1885/156202.
Full textAbstract:
Obesity has become one of the most fast-growing economic burdens in the world. It is associated with increased susceptibility to modern diseases, such as diabetes, cardiovascular diseases, and cancer. One of the common physiological changes in obese individuals is a chronic inflammatory state from increased circulating pro-inflammatory cytokines and adipokines, which are secreted from excessive adipose tissue. Human recombinant interleukin-1 receptor antagonist (IL-1Ra), commercially called Kineret (anakinra), has been prescribed to treat rheumatoid arthritis because it antagonises a pro-inflammatory signalling cascade of interleukin-1. Clinical studies on rheumatism and diabetes have shown that anakinra improved glucose homeostasis and the inflammatory state. This thesis has focused on the effect of anakinra on the diet-induced obesity (DIO) animal model with or without change in dietary fat content. In this study, DIO mimicked common obesity of humans by promoting fast body weight gains, increased fat proportions, and impaired glucose homeostasis. The animal study in this thesis support the notion that anakinra boost the positive effect of dieting but may not be effective in preventing further weight gain in DIO without restricting fat content in diet. With dietary change to regular diet, anakinra treatment helped reduce body weight in DIO by suppressing appetite and energy absorption without changing energy expenditure. In relation to obesity-related diabetic symptoms, in this study, only dietary change improved glucose intolerance in DIO. Anakinra also influenced adipokine profile, including resistin and adiponectin levels. Plasma leptin concentration reduced to normal by dietary change as a consequence of decreased amount of adipose tissue, whereas circulating levels of both resistin and adiponectin were lowered by anakinra. The effect of anakinra on lipid metabolism, however, was not significant. Anakinra could not offset the detrimental effects of high-fat diet in DIO without dietary correction. Peripheral anakinra administration did not reverse weight gains from excessive fat mass due to positive energy balance, glucose intolerance, hyperleptinaemia, and high blood cholesterol in DIO without dietary change. However, a low dose of anakinra alleviated weight gain in DIO by increasing energy expenditure. In conclusion, anakinra effectively helps converting DIO to the healthy state only when accompanied with proper dieting. Therefore, peripheral anakinra administration may potentially be supplementary to dieting in the treatment of common obesity.
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Lin, Kai-Wei, and 林凱瑋. "The role of Interleukin-1 Receptor Antagonist in Th1/Th2 Functional Differentiation." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/97054632666852747224.
Full textAbstract:
碩士國立臺灣大學
免疫學研究所
86
Naive T lymphocytes undergo priming when they first come into contact with foreign antigen, a process referred to as functional differentiation. This phenomenon is now believed to play an important role in the regulation of immune response phenotype on human beings. Therefore, it is important to know how to control the balance between two types of the helper T cells.So far it is known that IL-12 and IL-4 can direct Th1 and Th2 functional differentiation, respectively. Furthermore, Interleukin-1 is known to be able to maintain Th2 cells proliferation in vitro. However, the role of IL-1 in functional differentiation of naive helper T cells is still unknown! In!this study, we first demonstrated that if Na*ve T lymphocytes undergo priming without IL-1 can differentiate and produce high levels of IFN-g but low levels of IL-4 in second restimulation. In addition, we also found this process is depend on APCs but not strickly depend on IL-4. We also use the technique of in vivo gene transfection with cationic liposomes to induce IL-1ra overexpression in the site where specific immune response occured. IL-1ra can also promote antigen-specific IgG2a and IFN-g production in vivo. All of these results suggest that IL-1 can promote Th2-development. Thus, the balance between endogenous IL-1 and IL-1ra in primary immune responses is a key factor in determining the functional deviation of Th cells.
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Li, Chin-Ni, and 李錦妮. "Genetic polymorphism in interleukin-1B and interleukin-1 receptor antagonist on gastric cancer and duodenal ulcer." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/10054127008221444767.
Full textAbstract:
碩士國立中山大學
生物醫學科學研究所
90
Interleukin-1 (IL-1) is a prototypic multifunctional cytokine. IL-1 family include interleukin-1 a (IL-1 a), interleukin-1b (IL-1 b) and interleukin-1 receptor antagonist (IL-1 Ra). IL-1 b is the archetypeal pleiotropic cytokine which have been produced by many cells and exerting its biological effects on almost all cell types. IL-1 b is the most potent of known agents that are gastric cytoprotective, antiulcer, antisecretory and an inhibitor of gastric emptying. IL-1 Ra competes with IL-1 b for cell surface receptor occupancy. Host genetic factors that affect interleukin-1 (IL-1) have been reported to influence the susceptibility of Caucasians to gastric cancer. Whether Asians have the same genetic susceptibility remains unclear. In this study, the genetic associations of IL-1B and IL-1RN polymorphisms with gastric cancer and duodenal ulcer in Taiwan were evaluated. Genomic DNA from 140 unrelated Taiwanese patients with gastric adenocarcinoma, 94 with duodenal ulcer and 165 ethically matched healthy controls was typed for polymorphisms at positions —31, -511, and +3954 in the IL-1B gene, and the variable number of tandem repeats polymorphisms in intron 2 of the IL-1RN gene. The allele frequencies of IL-1RN 2R in gastric cancer cases were much higher than those in healthy controls (9% vs. 3%, p = 0.781). The allele frequencies of IL-1B —31, IL-1B —511 and IL-1B +3954 did not differ. An increased risk of the development of intestinal type gastric carcinoma was found in IL-1RN 2R carriers with an odds ratio (OR) of 4.06 (95% confidence interval [CI]: 1.68 — 9.79, p-value=0.085). And another increased risk of the development of diffuse type gastric carcinoma was found in IL-1RN 2R carriers with an odds ratio (OR) of 3.15 (95% confidence interval [CI]: 1.16 — 8.56, p-value=0.061). A significant association was found in IL-1RN 2R/4R genotype and the risk of the development of duodenal ulcer, with an odds ratio (OR) of 2.57 (95% CI: 1.03 — 6.38, p = 0.292). No significant relationship was noted in duodenal ulcer patients with IL-1B genotype examed in this study. Additionally, a synergistic interaction between blood type A and IL-1 RN 2R carriers existed in gastric cancer patients (OR= 4.51; 95% CI: 1.20 — 16.88, p-value=0.516). The synergistic interaction was even stronger between blood type O and IL-1 RN 2R carriers of duodenal ulcer patients (OR= 10.3; 95% CI: 2.10 — 50.61, p-value=0.160). In conclusion, the genetic polymorphisms of IL-1RN 2R and blood type A are associated with the development of gastric cancer. The genetic polymorphisms of IL-1RN 2R and blood type O are associated with the development of duodenal ulcer.
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Tsai, Shin-Chang, and 蔡信昌. "Evaluation of the Effects of Interleukin-1 Receptor Antagonist on Experimental IgA Nephropathy." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/57074124294268860345.
Full textAbstract:
碩士國防醫學院
病理學研究所
84
IgA腎病變(nephropathy)是一種由 IgA 免疫複合物所誘發的腎絲球疾病 。其主要病理特徵為腎絲球膈部有大量IgA和C3的沉積。本研究的主要目 的是以 IgA 腎病變之動物模式進行介白素 1 接受器拮抗劑( interleukin-1 receptor antagonist)之療效評估，以期建立理想的治療 模式。我們使用兩種動物模式，包括：被動誘發性(passively induced) IgA腎病變和自發性(spontaneous)IgA腎病變。被動誘發性IgA腎病變，是 以含有產生IgA抗體之TEPC-15融合瘤所的老鼠腹水和肺炎鏈球菌( Streptococcus pneumonia strain R36A)細胞壁抗原誘發 BALB/c小白鼠 產生IgA腎病變，代表一種短期而急性誘發之實驗性 IgA 腎病變，通常病 鼠之尿液會出現輕度蛋白尿，而且腎絲球會有明顯膈細胞增生現象。相對 的，自發性IgA腎病變是以ddY小白鼠為之；通常於飼養10個月左右，尿液 出現中度蛋白尿而且體內IgA抗體和腎絲球中IgA和C3的含量增加；電鏡檢 查可見膈細胞增生和膈基質增加的現象，電鏡緻密沉澱物只偶而出現於膈 部。我們以介白素1 接受器拮抗劑分別治療上述兩種IgA腎病變小白鼠。 療效之評估包括臨床表徵分析、實驗室檢查、及腎組織評估等。結果顯示 ：(1)被動誘發性IgA腎病變：評估 [51Cr]EDTA之清除能力及血清中肌酸 甘之濃度發現，治療組小白鼠之腎功能明顯改善。治療組小白鼠之腎絲球 細胞增生現象明顯降低。此外，治療組小白鼠之腎絲球中之desmin、 actin、collagen type Ⅳ、fibronectin、laminin 及介白素6 之表現亦 明顯降低。免疫螢光半定量分析結果顯示，治療組小白鼠之腎絲球中 IgA 及 C3 之沉澱量明顯減低。但無論治療組與未治療組之腎絲球之介白 素 1 及TGF-β之表現皆無統計學上明顯之差異。與上述結果相似，治療 組之ddY小白鼠之腎功能有明顯改善之現象。而且，治療組之ddY小白鼠出 現蛋白尿的程度亦明顯的減低。此外，治療組ddY小白鼠之腎絲球中之 desmin、actin、collagen type Ⅳ、fibronectin、 laminin 及介白素 6之表現亦明顯降低。但無論是治療組或未治療組之腎絲球中免疫沉澱物 、介白素1 及TGF-β之表現皆無統計學上明顯之差異。由實驗結果可推論 介白素1 接受器拮抗劑可改善實驗性IgA腎病變；前者之作用機轉可能是 經由其干擾介白素1 接受器拮抗劑抑制了介白素1 結合到腎組織中之接受 器進而抑制介白素1 於腎組織中所媒介之發炎作用。
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Fischer, Philipp [Verfasser]. "Inhibition of inflammatory vasculopathic processes by interleukin-1 receptor antagonist, transduced endothelial progenitor cells / Philipp Fischer." 2008. http://d-nb.info/990269345/34.
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Wei, Li-Chen, and 魏利真. "Prevention of Extraocular Myositis by Recombinant Adeno-asssociated Virus Vector With Delivary Of Interleukin-1 Receptor Antagonist." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/08597886528499910558.
Full textAbstract:
碩士中國醫藥大學
醫學研究所碩士班
95
Purpose: To evaluate the recombinant adeno-associated virus vector encoding interleukin-1 receptor antagonist (rAAV–IL-1Ra) complementary DNA for its potential in the prevention of phorbol ester–induced extraocular myositis. Methods: Gene delivery to superior recturs muscle was achieved through intramuscular injections of rAAV-IL-1 Ra in the left eyes and AAV expressing Escherichia coli LacZ (rAAV-LacZ) in the right eyes of white rabbit. After 3 weeks, phorbol ester was used to induce myositis, and the severity of myositis was evaluated. The synthesis and accumulation of IL-1Ra within the muscle were determined using immunohistochemistry and western blot analysis three weeks after gene delivery. The preventive effects of IL-1Ra were evaluated by strain measurement, histologic changes of muscle and inflammatory cell counts one week after myositis induction. Results: Gene expression of IL-1 Ra was demonstrated through immunohistochemistry and Western blot analysis. Histology revealed more inflammatory cells were retained in the rAAV- LacZ treated muscles (2594.386±319.933 cells/mm2; n=10) than in the rAAV- IL-1 Ra treated muscles (1369.479±228.509 cells/mm2; n=10). Strain measurement increased 150.4% 1 week after injection of phorbol ester in right eye, and increased 69.4% in the left eye with previous rAAV–IL-1Ra injection (p<0.01). The myositis in rAAV- IL-1 Ra treated muscles was less severe than that in the rAAV- LacZ treated muscles. Conclusion: This gene therapy, by combining highly efficient and stable rAAV gene delivery, and the anti-inflammatory effect of IL-1Ra, provides a valuable approach for prevention of extraoculor myositis.
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Kao, Chung-Hsuan, and 高崇旋. "Extract of Reishi polysaccharides-mediated signal transduction in the regulation of Interleukin-1 receptor antagonist in human monocytes." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/46985783573505794813.
Full textAbstract:
碩士國立陽明大學
醫學生物技術研究所
95
For years, Ganoderma lucidum (Reishi or Ling-zhi), has been widely used in Asian countries as therapeutic medicines to treat abnormality related to immunity. We have demonstrated that an extract of Reishi polysaccharides (EORP) exerting an immuno-modulating activities by stimulating inflammatory cytokines including interleukin-1 (IL-1). We recently reported that EORP dramatically increased interleukin-1 receptor antagonist (IL-1Ra), which compete with biological functions of IL-1, expression in mice model and human primary macrophages. In order to continue to investigate the mechanism of EORP induction of IL-1Ra expression, initially, we conducted the experiments of dose and time-course studies, and found IL-1Ra expression in both human primary monocytes and THP-1 monocytic cell lines. In addition, EORP was found to up-regulate IL-1Ra message RNA expression. Interestingly, via responding to EORP and LPS in genetic variation of murine macrophage HeNC2 and GG2EE cell lines, as well as using toll-like receptor-2 (TLR2) and -4 (TLR4) neutralizing antibodies blockage in human monocytes, we found that both TLR2 and TLR4 involved in the EORP-mediated IL-1Ra secretion. Using TLR-/- knockout mice, we found that reduction of EORP-induced IL-1Ra production in either TLR2-/- or TLR4-/- mice, indicating that incorporated of TLR2 and TLR4 involved in EORP-mediated IL-1Ra expression. We have found that EORP differentially modulates the protein kinase (PK)-mediated signal transduction pathways associated with anti-inflammatory cytokine, IL-1Ra expression. Specifically, EORP rapidly stimulated protein tyrosine kinase (PTK)-mediated phosphorylation, followed by induction of PKs such as phosphoinostitide 3-kinase (PI3K), phospholipase C (PLC), various PKC isoforms and activation of MAPKs: ERK, JNK and p38. Using PK inhibitors in the kinase activity assays, Western blot analyses and IL-1Ra ELISA, we have extensively examined and dissected the role of individual PK in the regulation of IL-1Ra. Our findings establish that initially, EORP binds to TLR2 and TLR4, followed by EORP-mediated signaling pathway: PTK/PI3K/PLC/PKCs/MEK1/ERK, which involved in the IL-1Ra regulation.
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Pillay, Visva. "Variants of inflammatory mediators: alpha-1-protease inhibitors, cortisol binding globulin, interleukin-1-receptor antagonist and beta-2-adrenergic receptor genes in atopic asthmatic and non-asthmatic South Africans." Thesis, 2014.
Find full textAbstract:
According to current concepts asthma is primarily an inflammatory condition of the
bronchi which results from the complex interactions between heterogenous genetic and
environmental factors. Although the environmental allergens are fairly well known, little
information concerning the genetic differences between atopic and non-atopic individuals
is available, A number of candidate genes have been proposed, including genes for
protease inhibitors, interleukins and the beta-2-adrenergic receptor ((32AR) The present
study was undertaken in order to determine whether molecular variation of certain atopy
candidate genes (alpha-1-protease inhibitor, cortisol binding globulin, interleukin-1-
receptor antagonist and p2AR) may be associated with atopic asthma in black and white
asthmatic South Africans. Alpha-1-protease inhibitor (ctjPI) has been implicated in the
pathogenesis of emphysema, if it is present in one of its deficient phenotypic forms. Given
that a ^ I is also an acute phase reactant in humans, it is possible that an association exists between the manifestations of asthma and a,PI or its deficiency. This investigation looked at the various phenotypes of cqPI in black and white asthmatic and control individuals by making use of isoelectric focusing as well as to make use of the polymerase chain reaction (PCR) which allowed for the identification of two haplotypes of the Ml phenotype ipf a,PI,viz. Ml (Ala213) and MI (Val213), There was a significant increase in the M l (Ala213) haplotype in the black groups as compared to a white groups. A novel finding was the identification of a new variant, the M1E(j0HANNESBURG)_ A significant difrerence was also found when comparing patients with severe asthma who had the rarer variants of a,PI as compared to mild or moderate asthmatic patients with the M1M1 phenotype indicating that UjPI plays a role in the pathogenesis of asthma.No mutation was found in exon 2 (an amino acid substitution in this exon was shown to be responsible for abnormal CBG steroid binding activity) of the cortisol binding
globulin (CBG), (as determined by sequencing analysis) in black and white asthmatic and
control individuals in the present study. However, taking the fact that CBG and oqPI share
more than 40% homology of amino acid sequence, it would be advisable to continue the
search for possible mutations in other exons of the gene which might act as markers for
mutations in other genes that are closely linked to the CBG and which play a role in
asthma.An important role player in the control of the inflammatory process could be the
IL-1 Ra since it is a powerful endogenous anti-inflammatory molecule that competitively
inhibits IL-1 a and IL-ip. The allelic frequency of the polymorphism in intron 2 of the IL-1
Ra gene was studied in black and white patients with asthma and control individuals, The
plasma IL1 Ra concentration was also determined using a standardised Elisa kit. No
significant differences in IL-1 Ra VNTR allelic frequencies were noted in the clinical
groups and controls in each of the two population groups, However the 410 bp allele was
increased in all black subjects as compared to all white subjects while the 240 bp allele was markedly reduced in all black subjects as compared to all white subjects. Significant
differences were observed when we compared the levels of severe patients with patients
classified as having mild astlima. Significant differences were also observed when
comparing moderate asthmatic children with the mild asthmatic children. Our results
indicate, a distinct racial difference in the EL-1 Ra gene polymorphism and although this
polymorphism is unlikely to be an important determinant of overall disease susceptibility
in asthma the IL-1 Ra plasma concentrations could act as a marker of disease severity in
asthmatic patients.The p2 adrenergic receptor (p2AI<) is an important factor in the control of the inflammatory process in asthma. The gly 16 polymorphism of the (32AR which appears to impart enhanced down regulation of receptor numbers has been found to have a higher prevalence in nocturnal white asthmatics. The allelic frequencies of the gly 16
polymorphism was studied in black and white asthmatic children control individuals.
Genotyping was performed by making use of PGR and the presence of the mutation was
analysed on agarose gels using ethidium bromide staining and confirmed by DNA
sequencing. There was no difference in the prevalence of the gly 16 polymorphism of the
(32AR between the black and white control individuals. There was a significant increase
in the frequency ofthe gly 16 polymorphism of the P2AR between severe and moderate
asthmatics. There was also a significant increase in the prevalence of the gly 16
polymorphism in those patients who required a long acting beta stimulant to gain
symptomatic control, We did not find a difference- in the prevalence of the gly 16
polymorphism between nocturnal vs. non-nocturnal asthmatics. The gly 16 polymorphism
of p2AR was predictive of more severe asthma in this study. It was also predictive for
those patients who needed a long acting beta stimulant to attain symptomatic control. This
polymorphism may act as a disease modifier in asthma and represents one of the many
genetic variables involved in the pathogenesis of asthma.
In conclusion, the present study demonstrates the extent and complexity of genetic
susceptibility to atopic asthma and it highlights the need for more refined association and
functional studies that will identify additional atopy'loci and their association with asthma.
Part of the work in this dissertation was the subject of conference p resentations.
Pillay V, Gaillard M.C., Dewar J.B, Hirsch G.P and Song E, “Differences in the
Interleukin-1 Receptor Antagonist (IL-IRa) Gene Polymorphism In Black And White
Patients With Asthma Or Rheumatoid Arthritis And Control Individuals.” 37"' Annual
Congress of the Federation of South African Societies of Pathology. Sea Point, Cape
Town. 29 June - 2 July 1997.
Pillay V, Gaillard M.C, Halkas A and Song E. “The GLY 16 Polymorphism of the P2
Adrenergic Receptor in South African Asthmatic Children.” Biochemistry In Africa: 2nd
Of) FASBMB and 15,h SASBMB. Potchefstroom, South Africa. 29 September - 3 October
1998.
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Lin, Juway, and 林周緯. "The multifaceted effects of polysaccharides isolated from Dendrobium huoshanense on immune functions with the induction of Interleukin-1 receptor antagonist (IL-1ra) in monocytes." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/73754702640535571297.
Full textAbstract:
博士國立臺灣大學
生化科學研究所
102
Abstract Dendrobium huoshanense is a valuable and versatile Chinese herbal medicine with the anecdotal claims of cancer prevention and anti-inflammation. However, its immunological activities are limited to in vitro studies on a few cytokines and immune cell functions. First, we investigated the effects of polysaccharides isolated from DH (DH-PS) on inducing a panel of cytokines/chemokines in mice in vivo and human in vitro. We found that DH polysaccharides (DH-PS) induced TH1, TH2, inflammatory cytokines and chemokines in mouse in vivo and human cells in vitro. Secondly, we demonstrated that DH-PS expanded mouse splenocytes in vivo including CD4+ T cells, CD8+ T cells, B cells, NK cells, NKT cells, monocytes/macrophages, granulocytes and regulatory T cells. Notably, DH-PS induced an anti-inflammatory molecule, IL-1ra, in mouse and human immune cells, especially monocytes. The serum level of IL-1ra elicited by the injection of DH-PS was over 10 folds of IL-1β, suggesting that DH-PS-induced anti-inflammatory activities might over-ride the inflammatory ones mediated by IL-1β. The signaling pathways of DH-PS-induced IL-1ra production was shown to involve ERK/ELK, p38 MAPK, PI3K and NFκB. Finally, we observed that IL-1ra level induced by DH-PS was significantly higher than that by F3, a polysaccharide extract isolated from another popular Chinese herbal medicine, Ganoderma lucidum. These results indicated that DH-PS might have potential applications for ameliorating IL-1-induced pathogenic conditions.
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Takes, Julia. "Der Einfluss von Interleukin-1 und des Interleukin-1-Rezeptorantagonisten (Anakinra) auf die epithelial-mesenchymale Transition von Tubulusepithelzellen in vitro." Doctoral thesis, 2011. http://hdl.handle.net/11858/00-1735-0000-0006-B25C-C.
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(9189491), Paula Cooper. "The Impacts of Inflammation on Adult Prostate Stem Cells." Thesis, 2020.
Find full textAbstract:
Adult prostate stem cells (PSC) are a rare epithelial progenitor population in the prostate. While essential for normal homeostasis, they have also been implicated in hyperplasia and cancer initiation. While studies have shown that inflammatory growth factors and cytokines can fuel stem cell expansion, the impact of inflammation on PSC is not well understood. To study the impact of inflammation on the prostate, the Ratliff laboratory developed the Prostate Ovalbumin Expressing Transgenic 3 (POET3), an inducible mouse model of abacterial T cell mediated prostate inflammation, which functions as a model for human autoimmune prostatitis. Previous studies using the POET3 demonstrated that inflammation increased proliferation and differentiation of PSC enrichments. Based on these findings, it was speculated that inflammation impacts prostate stem cells to enhance mechanisms of survival, possibly as a means of tissue protection.
Since androgen receptor (AR) signaling is the major driver of cellular differentiation and survival in the prostate, it was further hypothesized that inflammation promotes AR signaling in the PSC. To address this hypothesis, PSC and their resulting organoids from inflamed and non-inflamed (naïve) POET3 mice as well as human patient samples were assessed for AR and its signaling components.
These data were expanded by single cell mRNA sequencing using Fluidigm’s C1 platform, which revealed changes in stem cell populations, differential expression of interleukin 1 alpha (IL-1⍺) and its signaling components, and upregulation of various genes associated with immune regulation. Thus, experiments described herein probed the impacts of inflammation on AR, IL-1⍺, and T cell regulatory abilities in the PSC.
The results of these studies indicate that indeed, inflammation increases PSC survival. Inhibition of IL-1⍺ via inflammation-mediated up-regulation of IL-1 receptor antagonist (IL-1RA) promotes AR signaling, resulting in proliferation, differentiation, and AR target gene expression which can be modulated by Enzalutamide (a clinical AR inhibitor). Furthermore, PSC from inflamed mice are able to suppress cytotoxic T cell function in ex vivo assays. These studies set the foundation for new ways to treat proliferative diseases of the prostate by targeting IL-1⍺, AR, and immune regulation in the PSC.
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Pierre, Wyston Chadwick. "Développement d’une nouvelle stratégie neuroprotectrice efficace et d’une méthode de quantification précoce non invasive des lésions de la matière blanche cérébrale immature sur un modèle animal." Thesis, 2020. http://hdl.handle.net/1866/25554.
Full textAbstract:
Les grands prématurés sont particulièrement vulnérables aux lésions inflammatoires de la substance blanche (WMI) qui augmentent le risque de troubles cognitifs et neurodéveloppementaux à long terme dans cette population. L’utilisation de l’imagerie par résonance magnétique (IRM) dans cette population a permis une évaluation non invasive de la progression des WMI et une meilleure compréhension de la pathologie. Les WMI sont associées une activation de la microglie et des astrocytes et la production de facteurs pro-inflammatoires, dont l’interleukine 1 (IL-1).
En utilisant un modèle de WMI induite par injection intracérébrale de lipopolysaccharides (LPS), nous avons évalué dans un premier temps les changements de méthylation de l’ADN durant la phase aigüe (24 h) et la phase chronique (21 jours) de l’inflammation. Par la suite, nous avons déterminé la capacité de l’IRM multimodale de détecter la lésion et la réponse thérapeutique à un antagoniste du récepteur de l’IL-1. Finalement, par le biais d’un antagoniste et d’un modulateur allostérique du récepteur à l’IL-1, nous avons évalué in vitro le rôle de la signalisation IL-1 durant la phase aigüe de la modulation de l’activation de la microglie et des astrocytes par le LPS.
Nous avons démontré la présence d’une altération du méthylome cérébral dans divers mécanismes liés au neurodéveloppement et à la réponse immunitaire. De plus, l’application de l’IRM multimodale dans notre modèle a permis d’évaluer in vivo la lésion et le début de la réponse thérapeutique durant la phase aigüe (24 h) de l’inflammation. L’évaluation à l’IRM corrèle aux changements observés par immunomarquage post mortem. In vitro, le LPS induit une réponse mixte de la microglie et des astrocytes qui évoluent dans le temps vers une réponse pro-inflammatoire et neurotoxique. Bien que l’IL-1 est hautement exprimée par la microglie et les astrocytes, son inhibition a un effet limité sur la modulation de l’activation gliale dû à la multitude de voies activées par le LPS durant la phase aigüe de l’inflammation.Very premature infants are particularly vulnerable to inflammatory white matter injury (WMI) which increases the risk of long-term cognitive and neurodevelopmental disorders in this population. The use of magnetic resonance imaging (MRI) in this population has allowed non-invasive assessment of the progression of WMI and a better understanding of the pathology. WMI is associated with activation of microglia and astrocytes and the production of pro-inflammatory mediators, including interleukin 1 (IL-1). Using a model of inflammatory WMI induced by intracerebral injection of lipopolysaccharides (LPS), we first evaluated the changes in DNA methylation during the acute phase (24 h) and the chronic phase (21 days) of inflammation. We then determined the ability of multimodal MRI to detect the lesion and the therapeutic response to an IL-1 receptor antagonist. Finally, using an antagonist and an allosteric modulator of the IL-1 receptor, we evaluated in vitro the contribution of IL-1 signaling during the acute phase of the modulation of microglia and astrocytes activation by LPS. We have shown the presence of persistent alteration DNA methylation profile in the brain that was associated with pathways involved in neurodevelopment and immune response. In addition, the application of multimodal MRI in our model made it possible to evaluate in vivo the lesion and the therapeutic response during the acute phase (24 h) of the inflammation. The changes at the MRI correlated to post-mortem evaluation by immunostaining. In vitro, LPS induce a mixed response of microglia and astrocytes which evolved over time toward a pro-inflammatory and neurotoxic phenotype. Although IL-1 is highly expressed by microglia and astrocytes, its inhibition has a limited effect on the modulation of glial activation due to the multitude of pathways activated by LPS during the acute phase of inflammation.
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"The role and mechanism of the pro-inflammatory cytokine IL-1 Beta on megakaryocytopoiesis: the expression of IL-1 receptors and signal transduction pathway." 2001. http://library.cuhk.edu.hk/record=b5890895.
Full textAbstract:
by Chuen Ka Yee.Thesis (M.Phil.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (leaves 134-166).
Abstracts in English and Chinese.
ACKNOWLDEGEMENT --- p.ii
PUBLICATIONS --- p.iii-iv
ABBREVIATIONS --- p.v-viii
INDEX FOR FIGURES --- p.ix xii
INDEX FOR TABLES --- p.xiii
ABSTRACT (Chinese and English) --- p.xiv-xvi
TABLE OF CONTENT --- p.xvii
Chapter 1. --- INTRODUCTION --- p.1-37
Chapter 2. --- OBJECTIVES --- p.38-40
Chapter 3. --- METHODS AND MATERIALS --- p.41 -70
Chapter 4. --- RESULTS AND DISCUSSION --- p.71-130
Chapter 5. --- GENERAL DISCUSSION AND CONCLUSION --- p.131-133
BIBLIOGRAPHY --- p.134-166