Rönnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B
Department of Clinical Immunology, Rudbeck Laboratory, University Hospital, Uppsala University, S-751 85 Uppsala, Sweden.
Ann Rheum Dis. 2003 Jan;62(1):37-42. doi: 10.1136/ard.62.1.37.
Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors.
To investigate whether circulating SLE ICs stimulate type 2 cytokine production.
Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcgammaR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcgammaR expression and IC-induced cytokine production.
Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 v 1.25 spot forming cells/50 000 PBMC; p<0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcgammaRII antibodies, and the FcgammaRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6.
SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcgammaRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.
白细胞介素（IL）-6和IL-10水平升高被认为通过增强自身抗体产生和免疫复合物（IC）形成，促进系统性红斑狼疮（SLE）的发病机制。这些免疫复合物随后可通过Fc和补体受体刺激细胞反应。
研究循环中的SLE免疫复合物是否刺激2型细胞因子产生。
将20份活动期SLE患者的血清样本与18份健康对照者的血清进行比较。将血清及血清中的聚乙二醇（PEG）沉淀物加入外周血单个核细胞（PBMC）培养物中，采用酶联免疫斑点法（ELISPOT）和酶联免疫吸附测定法（ELISA）研究IL-10和IL-6的产生情况。在阻断实验中使用Fcγ受体（FcγR）抗体，采用流式细胞术评估单核细胞FcγR表达与IC诱导的细胞因子产生之间的相关性。
与对照血清相比，10%稀释的SLE血清诱导产生IL-10的细胞数量显著增加（中位数，11.75对1.25个斑点形成细胞/50 000个PBMC；p<0.0001）。与对照PEG沉淀物相比，SLE血清中的PEG沉淀物也诱导IL-10（p=0.0l6）和IL-6（p=0.042）水平显著升高。SLE PEG沉淀物或人工IC诱导的IL-10产生可被抗FcγRII抗体阻断，CD14+单核细胞上的FcγRII表达与IC诱导的IL-10和IL-6产生相关。
SLE血清刺激PBMC产生IL-10和IL-6，这种效应至少部分由可沉淀的IC通过FcγRII起作用来解释。这种效应为SLE中IL-10产生增加提供了一种可能机制，即B细胞活化、抗体产生、IC刺激单核细胞/巨噬细胞以及2型细胞因子形成恶性循环，这可能有助于维持SLE中B细胞的高活性。
