Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships.

ABSTRACT

Although the administration of a fixed dose of the alpha-interferon (alpha-IFN) inducer, polyinosinic polycytidilic acid (poly IC), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly IC with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly IC with the induction of serum alpha-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 IC-treated normal Wistar rats is attributable to a deficient alpha-IFN response. Using poly IC doses of 0.5, 1.5, 5, and 10 micrograms/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum alpha-IFN response. Moreover, all doses of poly IC accelerated the onset of diabetes in BB rats. Serum alpha-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum alpha-IFN were associated with earlier onset of diabetes (P < 0.001). Poly IC-induced serum alpha-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly IC significantly increased serum alpha-IFN levels, diabetes was not induced. The results of this study indicate that poly IC administration elevates serum alpha-IFN and accelerates the development of diabetes in BB rats at even very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)