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681.
Yanaba K Yoshizaki A Asano Y Kadono T Tedder TF Sato S 《The American journal of pathology》2011,178(2):735-743
B cells mediate multiple functions that influence immune and inflammatory responses. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to immediate intestinal injury. Dextran sulfate sodium-induced intestinal injury serves as an experimental animal model for human ulcerative colitis. The contribution of B cells to DSS-induced intestinal injury is unclear. In this study, we show that DSS-induced intestinal injury was more severe in CD19-deficient (CD19(-/-)) mice than in wild-type mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1% to 2% of splenic B220(+) cells in wild-type mice. Remarkably, adoptive transfer of these B10 cells from wild-type mice reduced inflammation in CD19(-/-) mice in an IL-10-dependent manner. These results demonstrate that IL-10 production from regulatory B10 cells regulates DSS-induced intestinal injury. These findings may provide new insights and therapeutic approaches for treating ulcerative colitis. 相似文献
682.
Inflammatory abdominal aortic aneurysms (IAAAs) represent 3% to 10% of all AAAs. However, inferior vena cava occlusion secondary to an IAAA is rarely reported. We report a case of inferior vena cava occlusion secondary to an IAAA presenting deep venous thrombosis. As it is crucial to avoid pulmonary embolism and excessive blood loss during an operation, we pre-operatively implanted a venous filter and minimized intra-operative dissection that allowed successful operative repair. 相似文献
683.
684.
E. H. S. Choy D. A. Isenberg T. Garrood S. Farrow Y. Ioannou H. Bird N. Cheung B. Williams B. Hazleman R. Price K. Yoshizaki N. Nishimoto T. Kishimoto G. S. Panayi 《Arthritis \u0026amp; Rheumatology》2002,46(12):3143-3150
Objective
To investigate the safety and efficacy of MRA, a recombinant human anti–interleukin‐6 (anti–IL‐6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL‐6, in patients with established rheumatoid arthritis (RA).Methods
A randomized, double‐blind, placebo‐controlled, dose‐escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment.Results
Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1‐ and 1‐mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C‐reactive protein values fell significantly in the 5‐ and 10‐mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1‐, 1‐, 5‐, and 10‐mg/kg MRA cohorts, respectively) required corticosteroid or disease‐modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1‐, 1‐, and 10‐mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug.Conclusion
This is the first randomized controlled trial showing that inhibition of IL‐6 significantly improved the signs and symptoms of RA and normalized the acute‐phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.685.
Hiroyuki Takemura Hiroshi Suzuki Kazuyuki Yoshizaki Atsushi Ogata Takamichi Yuhara Takao Akama Kazuhide Yamane Heihachiro Kashiwagi 《Arthritis \u0026amp; Rheumatology》1992,35(8):940-943
Objective. To investigate the presence and the roles of anti–interleukin-6 (anti–IL-6) autoantibodies in rheumatic diseases, and to further elucidate clinical and pathophysiologic significance of anticytokine autoantibodies. Methods. Anti–IL-6 IgG autoantibodies were measured by the 125I–IL-6 binding activity of IgG, which was isolated from serum by protein A–Sepharose. Results. Nine of 52 sera (17.3%) from patients with systemic sclerosis (SSc) contained anti–IL-6 antibodies, whereas only 1.9% of sera from normal subjects and 0–5% of sera from patients with other rheumatic diseases were positive for the antibodies. Moreover, anti–IL-6 autoantibodies were found predominantly among patients with the limited form of SSc (42.9%), compared with those with the diffuse form (7.9%). Conclusion. Anti–IL-6 IgG autoantibodies were detected in patients with SSc, particularly those with the limited form of the disease, at a significantly increased frequency compared with normal subjects and patients with other rheumatic diseases. These results suggest that the development of anti–IL-6 autoantibodies and IL-6 may have a role in the pathophysiology of SSc. 相似文献