Kimura T, Suzuki K, Inada S, Hayashi A, Saito H, Miyai T, Ohsugi Y, Matsuzaki Y, Tanaka N, Osuga T
Animal Centre for Biomedical Research, Faculty of Medicine, University of Tokyo, Japan.
Clin Exp Immunol. 1994 Mar;95(3):525-9. doi: 10.1111/j.1365-2249.1994.tb07030.x.
We examined the effect of IL-6 on the development of autoimmune diseases (primary biliary cirrhosis, Sjögren's syndrome) employing murine graft-versus-host reaction (GVHR) model with MHC class II disparity. For this purpose, we used IL-6 transgenic (B6.6) mice in which a high level of IL-6 was detected. C57Bl/6 (B6) spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice ((bm12 x B6.6)F1) and GVHR with MHC class II disparity was induced. The transgenic hybrid mice with GVHR showed a larger spleen index and contained a higher serum level of IL-6 than those without GVHR. Autoimmune-like lesions in transgenic recipients became weakened compared with those in non-transgenic (bm12 x B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12 x B6.6)F1 GVHR group were significantly higher than that of (bm12 x B6)F1 GVHR group. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases.
我们采用具有MHC II类差异的小鼠移植物抗宿主反应（GVHR）模型，研究白细胞介素-6（IL-6）对自身免疫性疾病（原发性胆汁性肝硬化、干燥综合征）发展的影响。为此，我们使用了检测到高水平IL-6的IL-6转基因（B6.6）小鼠。将C57Bl/6（B6）脾T细胞注入与B6.C-H-2bm12（bm12）突变小鼠交配的B6.6小鼠（（bm12×B6.6）F1）中，诱导具有MHC II类差异的GVHR。与没有GVHR的转基因杂交小鼠相比，发生GVHR的转基因杂交小鼠脾脏指数更大，血清IL-6水平更高。与非转基因（bm12×B6）F1受体小鼠相比，转基因受体小鼠中的自身免疫样病变有所减弱。相反，（bm12×B6.6）F1 GVHR组的抗线粒体抗体水平显著高于（bm12×B6）F1 GVHR组。这些结果表明，体内过量产生的IL-6可能调节自身免疫性疾病的进展。
