Screening of biological response modifiers (BRMs) for preventive effects on type 1 diabetes mellitus in animal models.

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We previously reported that a streptococcal preparation (OK-432), a non-immunosuppressive biological response modifier (BRM), inhibited insulitis and development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats as animal models of IDDM. In this study we screened other BRMS, which were clinically used or possibly to be used, for the possible preventive effects on IDDM of the animal models.Fifteen kinds of BRMs were screened. Three from the bacteria origin; OK-432, N-CWS and LPS: four from the plant origin; Lentinan, PSK, Glycyrrhizin and Ubenimex; one synthetic product; Lobebzarit disodium (CCA); seven recombinant cytokines; human IL-1alpha , human IL-2, human TNFalpha, mouse TNFalpha , human TNFbeta , mouse IFNgamma, mouse GM-CSF.Of non-eytokine BRMS, OK-432, LPS and Lentinan strongly inhibited development of IDDM in NOD mice. N-CWS had the weak inhibitory effects. PSK, Glycyrrhizin, Ubenimex and CCA had no suppressive effects on the NOD mice diabetes, although the optimal dose was not examined enough. Only human and mouse TNFalpha out of the various cytokines significantly suppressed IDDM in NOD mice. However, the dose-effect of the other cytokines was not thoroughly evaluated. The effect of TNFbeta is in progress. OK-432 and TNFalpha had the inhibitory effect on diabetes in both NOD mice and BB rats.These results indicate that the various BRMs have possible therapeutic effects on human IDDM and that the environmental factors of bacteria and plant origins may have the inhibitory effects on the genetically-determined IDDM.