Katsikis P D, Chu C Q, Brennan F M, Maini R N, Feldmann M
Kennedy Institute of Rheumatology, Hammersmith, London, UK.
J Exp Med. 1994 May 1;179(5):1517-27. doi: 10.1084/jem.179.5.1517.
The presence and the role of interleukin 10 (IL-10), a potent cytokine synthesis inhibitory factor and antiinflammatory cytokine, were investigated in rheumatoid arthritis (RA). The expression of both mRNA and protein for IL-10 could be demonstrated in RA and osteoarthritis (OA) joints. Human IL-10 mRNA could be demonstrated by polymerase chain reaction amplification of cDNA made by reverse transcription of total RNA extracted directly from synovial tissue in five out of five RA and four out of five OA patients. IL-10 protein was demonstrated by specific immunoassay and immunohistology. IL-10 protein was spontaneously produced in all 11 RA and 17 OA synovial membrane cultures investigated, and this production was sustained for up to 5 d in culture in the absence of any extrinsic stimulation. IL-10 protein could also be detected by immunohistology in all five RA and four OA synovial membrane biopsies investigated, but not three normal synovial membranes. Immunohistology revealed that the IL-10 was localized to the synovial membrane lining layer and mononuclear cell aggregates. Immunofluorescence double staining revealed that the sources of IL-10 were monocytes in the lining layer, and T cells in the mononuclear cell aggregates. We found evidence that the IL-10 expression was functionally relevant, as neutralization of endogenously produced IL-10 in the RA synovial membrane cultures resulted in a two- to threefold increase in the protein levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1 beta, although IL-6 and IL-8 levels were not affected. The addition of exogenous recombinant IL-10 to the RA synovial membrane cultures resulted in a two- to threefold decrease in the levels of TNF-alpha and IL-1 beta. IL-8 levels were reduced by day 5; however, IL-6 levels were not affected by exogenous IL-10. Neutralization of the endogenous IL-10 in two out of seven RA synovial membrane cultures resulted in the expression of detectable levels of interferon gamma (561-1,050 pg/ml). Taken together, the above findings suggest that IL-10 is spontaneously produced in RA and OA and is an important immunoregulatory component in the cytokine network of RA, regulating monocyte and in some cases T cell cytokine production.
在类风湿性关节炎（RA）中研究了白细胞介素10（IL - 10）的存在及其作用，IL - 10是一种强效的细胞因子合成抑制因子和抗炎细胞因子。在RA和骨关节炎（OA）关节中均可证明IL - 10的mRNA和蛋白质表达。通过聚合酶链反应扩增从滑膜组织直接提取的总RNA逆转录制成的cDNA，在5例RA患者中的5例以及5例OA患者中的4例中可证明人IL - 10 mRNA。通过特异性免疫测定和免疫组织学证明了IL - 10蛋白。在所研究的所有11例RA和17例OA滑膜培养物中均自发产生IL - 10蛋白，并且在没有任何外部刺激的情况下，这种产生在培养中可持续长达5天。在所研究的5例RA和4例OA滑膜活检组织中，通过免疫组织学也可检测到IL - 10蛋白，但在3例正常滑膜中未检测到。免疫组织学显示IL - 10定位于滑膜衬里层和单核细胞聚集处。免疫荧光双重染色显示IL - 10的来源是衬里层中的单核细胞和单核细胞聚集处的T细胞。我们发现有证据表明IL - 10表达具有功能相关性，因为在RA滑膜培养物中中和内源性产生的IL - 10导致促炎细胞因子肿瘤坏死因子α（TNF - α）和IL - 1β的蛋白质水平增加两到三倍，尽管IL - 6和IL - 8水平未受影响。向RA滑膜培养物中添加外源性重组IL - 10导致TNF - α和IL - 1β水平降低两到三倍。IL - 8水平在第5天时降低；然而，IL - 6水平不受外源性IL - 10影响。在7例RA滑膜培养物中的2例中中和内源性IL - 10导致可检测水平的干扰素γ（561 - 1,050 pg/ml）表达。综上所述，上述发现表明IL - 10在RA和OA中自发产生，并且是RA细胞因子网络中的重要免疫调节成分，调节单核细胞以及在某些情况下T细胞的细胞因子产生。
