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Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 2006; 54:2817-2829. Clinical trial to determine safety and efficacy of IL-6 receptor antagonist as therapy for rheumatoid arthritis. Severe infections were only observed in groups treated with the antagonist (with or without methotrexate); the numbers of patients and duration of the study (16 weeks) was too short to determine infection risk, however.
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Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006; 295:2275-2285. A very thorough meta-analysis of the risk of developing malignancies or severe infections as reported in clinical trials with TNF-blockers in patients with rheumatoid arthritis. The odds ratios calculated were 3.3 and 2.0, respectively.
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Deutschman CS, Cereda M, Ochroch EA, Raj NR. Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6-/- mice. Crit Care Med 2006; 34:2613-2620. In a sepsis model using cecal ligation and puncture, male IL-6-/- mice rapidly succumbed (90% within 72 h) and, in a severe sepsis model using double puncture, all IL6-/- mice died within 12 h. The study shows the essential role of IL-6 in controlling/modulating the septic response and in hepatic regeneration.
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