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类风湿性滑膜中白细胞介素-1受体拮抗剂/白细胞介素-1β的平衡及其受白细胞介素-4和白细胞介素-10的调节

Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its regulation by IL-4 and IL-10.

作者信息

Chomarat P, Vannier E, Dechanet J, Rissoan M C, Banchereau J, Dinarello C A, Miossec P

机构信息

Laboratory for Immunologic Research, Schering-Plough, Dardilly, France.

出版信息

J Immunol. 1995 Feb 1;154(3):1432-9.

PMID:7822808
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.

摘要

研究了类风湿关节炎(RA)滑膜中白细胞介素-1β(IL-1β)和白细胞介素-1受体拮抗剂(IL-1Ra)的自发产生,以及IL-4和IL-10对其产生的调节作用。分别采用酶联免疫吸附测定法(ELISA)和放射免疫测定法(RIA)检测了19例RA患者滑膜组织培养块上清液中IL-1β和IL-1Ra的产生情况。培养10天后,IL-1Ra的自发产生量为1.42±0.43 ng/ml/100 mg滑膜,而IL-1β的自发产生量为4.03±0.90 ng/ml/100 mg滑膜(n = 19)。添加IL-4可使IL-1β的产生减少2.3倍(p = 0.001),使IL-1Ra的产生增加2.8倍(p = 0.003)。IL-10对IL-1Ra的产生无显著影响,但可抑制IL-1β的产生(主要在产生高水平IL-1β的样本中)。然而,IL-10在抑制IL-1β产生方面的作用不如IL-4强。IL-1Ra主要由类风湿滑膜单核细胞/巨噬细胞产生。在诱导从RA滑膜以及RA血液中纯化的单核细胞/巨噬细胞产生IL-1Ra方面,IL-4比IL-10更有效。因此,RA滑膜的特征是IL-1Ra和IL-1β产生之间失衡,有利于后者。IL-4以及程度较轻的IL-10可使这种平衡向有利于抗炎的方向转变。

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