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Autoimmune MRL/Mp-lpr/Ipr (MRL/l) mice were treated with the immunostimulating anti-cancer drug OK-432 (a streptococcal preparation), a potent inducer of tumour necrosis factor. Treatment was initiated at 8 weeks of age. before the onset of the autoimmune disease. OK.-432 prevented the development of immune complex-mediated gloraerulonephritis in a dose-dependent manner, and prolonged the life in this strain of mice. At 36 weeks of age, the incidence of proteinuria was 90% in the controls, 60% in the 0.5-KE( 1KE = 0.1 mg) treatment group, and 33% in the 20-KE group. The 50% survival time was 23 weeks for the controls: 32 weeks for the 0.5-KE group; and > 36 weeks for the 2.0-KE group. Immune complex deposition in glomeruli was significantly reduced in the treated groups. The IgM class of serum autoantibody levels was significantly increased by OK-432 treatment but the IgG class was almost unchanged. Furthermore, lymphadenopathy and splenomegaly were not suppressed. The results indicate that OK-432 may be useful in the treatment of autoimmune disease in humans. [ABSTRACT FROM AUTHOR]

We have previously reported that B cell abnormality in NZB/W F1 mice developed independently of thymus, Here we examined further whether B cells from NZB/W Fl mice respond to interlcukin-6 (IL-6), a factor for terminal differentiation of B cells. When freshly isolated splenic B cells were incubated for 5 days in the presence of human IL-6, an increased production of both IgM and IgG, including anti-DNA antibody, was evident in NZB/W Fl mice; there was no increase in BALB/c mice. A magnitude of augmentation in IgG but not IgM production by IL-6 became more apparent in older NZB/W FI mice. The increased immunoglobulin production seen with IL-6 was neutralized by treatment with rabbit anti-recombinant human IL-6 antibody. As B cells from athymic NZB/W Fl nude mice also responded to IL-6, it was suggested that B cells in NZB/W Fl mice differentiated into the IL-6-responding state in a thymus-independent manner. This B cell abnormality may be associated with the pathogenesis of autoimmune disease in NZB/W Fl mice. [ABSTRACT FROM AUTHOR]

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. C57B1/6 (B6) spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice ((bm12 × 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 contained with those in non-transgenic (bm12 × B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12 × B6.6)F1 GVHR group were significantly higher than that of (bm12 × B6.6)F1 GVHR group. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases. [ABSTRACT FROM AUTHOR]