Kawashima Masanori, Miossec Pierre
Department of Immunology and Rheumatology and INSERM U-403, Pavillon F, Hospital Edouard Herriot, 69437 Lyon Cedex 03, France.
Arthritis Res Ther. 2004;6(1):R39-R45. doi: 10.1186/ar1020. Epub 2003 Nov 4.
Inflamed synovium of rheumatoid arthritis (RA) has been associated with a T helper (Th)1 cytokine profile but the blood situation remains to be clarified. We studied the differential IFN-gamma producing activity of peripheral blood mononuclear cells (PBMCs) from RA patients (RA-PBMCs) and from healthy controls (H-PBMCs) in response to IL-12 and IL-18. RA-PBMCs had a decreased IFN-gamma production in response to IL-12 and IL-18 when compared with H-PBMCs. RA-PBMCs activated with phytohemagglutinin and phorbol 12-myristate 13-acetate showed an increased sensitivity to IL-12 and IL-18, but still the RA-PBMC response was lower. IL-18 increased IL-12-stimulated IFN-gamma production from RA synovium cells obtained after collagenase digestion more effectively than that of RA- or H-PBMCs. A specific inhibitor of IL-18 bioactivity, IL-18-binding protein (IL-18BP), down-regulated IL-12-induced IFN-gamma production by RA- or H-PBMCs and had a remarkable effect on RA synovium cells. In conclusion, RA disease combines a polarized immune response with an active Th1 in inflamed joints and a reduced Th1 pattern in peripheral circulation.
类风湿关节炎（RA）的炎症滑膜与辅助性T（Th）1细胞因子谱相关，但血液中的情况仍有待阐明。我们研究了类风湿关节炎患者外周血单个核细胞（RA - PBMCs）和健康对照者外周血单个核细胞（H - PBMCs）对白细胞介素 - 12（IL - 12）和白细胞介素 - 18（IL - 18）的干扰素 - γ（IFN - γ）产生差异活性。与H - PBMCs相比，RA - PBMCs对IL - 12和IL - 18的IFN - γ产生减少。用植物血凝素和佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯激活的RA - PBMCs对IL - 12和IL - 18的敏感性增加，但RA - PBMCs的反应仍然较低。IL - 18比RA - PBMCs或H - PBMCs更有效地增加了胶原酶消化后获得的RA滑膜细胞中IL - 12刺激的IFN - γ产生。IL - 18生物活性的特异性抑制剂IL - 18结合蛋白（IL - 18BP）下调了RA - PBMCs或H - PBMCs中IL - 12诱导的IFN - γ产生，并且对RA滑膜细胞有显著影响。总之，RA疾病在炎症关节中表现为极化免疫反应与活跃的Th1细胞并存，而在外周循环中Th1模式减弱。
