Induction of autoimmune disease by graft-versus-host reaction across MHC class II difference: modification of the lesions in IL-6 transgenic mice.

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.