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

Abstract

SUMMARY 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 (P<0.01) and in mice treated with control serum (P<002). This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P<0.01) and surface-Ig+ (S-Ig+) cells increased (P<0.05), whereas the proliferative response of spleen cells to concanavalin A (P< 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.