Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice

We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.