Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system
Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system
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DOI：
10.1111/j.1365-2249.2004.02569.x
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发表时间：
2004-09-01
影响因子：
4.6
通讯作者：
Rönnelid, J
中科院分区：
文献类型：
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作者：
Tejde, A;Mathsson, L;Rönnelid, J
免疫复合物（IC）可诱导体外细胞因子的产生。虽然由热聚集γ球蛋白（HAGG）组成的免疫聚集体（IA）作为模型IC增加了天然人血清培养细胞中白细胞介素(IL)-10的水平，但抑制了IL-12p40/p70的产生。三个系列的实验表明，IA对IL-12产生的影响依赖于功能完整的补体系统：(1)血清热失活逆转了IA对IL-12p40/p70产生的抑制作用；(2)添加C4可降低ia诱导的C4缺陷血清中IL-12p40的产生；(3)加入抑制C3激活的肽compstatin，模拟热失活对IL-12p40水平的影响。IL-12的中和导致IL-10水平适度增加，而IL-10的中和对IL-12p40的产生没有影响。ia诱导的IL-10的产生被抗Fcgamma RII抗体部分阻断，而Fcgamma R或CR阻断对IL-12p40的产生没有影响。IC和局部或全身补体激活是类风湿关节炎、系统性红斑狼疮和许多恶性肿瘤的特征。在这些疾病中，对IL-10和IL-12产生不同和补体依赖性的影响可能是重要的，在这些疾病中，控制补体系统可能是指导ic诱导的细胞因子产生1型或2型方向的一种方法。
Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcgamma RII antibodies, whereas Fcgamma R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.