Possible involvement of IL-12 in reovirus type-2-induced diabetes in newborn DBA/1 mice

This study extends our previous observations that the reovirus type-2(Reo-2) can induce autoimmune insulitis, which may be mediated by T-helper (Th) 1-dependent mechanisms, resulting in diabetes in newborn DBA/1 mice. In this study mRNA expression for Th1-related cytokines including Th1 and Th2 cytokines in splenic cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in relation to the development of insulitis. Furthermore, the effect of monoclonal antibody (MoAb) against interleukin (IL)-12(p40) on the development of insulitis and the mRNA expression in the splenic cells was examined. The mRNA expression for IL-12(p40), IL-18, and interferon (IFN)-gamma, but not IL-5, increased in the spleen in parallel with the development of insulitis. The treatment with MoAb to IL-12(p40) reduced the insulitis with diabetes which was associated with a decrease in the mRNA expression for IL-12(p40), IL-18 and IFN-gamma, and an increase of IL-4 mRNA expression in the spleen. The present study suggested that Th1-dominant systemic immune responses, being responsible for the development of autoimmune insulitis, might be induced by IL-12-induced and IL-18-activated mechanisms.