Although the administration of a fixed dose of the α-interferon (α-IFN) inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly I:C with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly I:C with the induction of serum α-IFN and the development of diabetes in DP-BB and normal Wistar rats. Also tested in this study is the hypothesis that the lack of development of diabetes in poly I:C-treated normal Wistar rats is attributable to a deficient α-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10 μ/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum α-IFN response. Moreover, all doses of poly I:C accelerated the onset of diabetes in BB rats. Serum α-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum α-IFN were associated with earlier onset of diabetes (P < 0.001). Poly I:C-induced serum α-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly I:C significantly increased serum α-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum α-IFN and accelerates the development of diabetes in BB rats at even very low doses. This finding in conjunction with the correlation of serum α-IFN with the onset of diabetes is consistent with a pathogenetic role of α-IFN. The absence of a diabetogenic effect of poly I:C in Wistar rats suggests that α-IFN alone cannot induce diabetes in this animal.

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