Topic
Interleukin 1 receptor antagonist
About: Interleukin 1 receptor antagonist is a research topic. Over the lifetime, 1740 publications have been published within this topic receiving 100563 citations. The topic is also known as: DIRA & ICIL-1RA.
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TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
4,354 citations
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TL;DR: The recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches and reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.
2,307 citations
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TL;DR: The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation.
Abstract: Background The expression of interleukin-1–receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1β in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis. Methods In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1–receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic–euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers. Results At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P = 0.03); C-peptide secretion was enhanced (P = 0.05), and there were reductions in the ratio of proinsulin to insulin (P = 0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P = 0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drugrelated serious adverse events. Conclusions The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation. (ClinicalTrials.gov number, NCT00303394.)
1,621 citations
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TL;DR: Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function.
Abstract: Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.
1,475 citations
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TL;DR: Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes and partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein.
Abstract: Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes. Partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein. The protein binds to the interleukin-1 receptor but has no interleukin-1-like activity, even at very high concentrations, and is therefore a pure receptor antagonist.
1,153 citations