Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice

Abstract
We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-α), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-γ) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (PP+ or CD8+ spleen cells decreased (P+ (S-Ig+) cells increased (PP< 0.01) and lipopolysaccharide (P<0.05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF.