Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships.
Although the administration of a fixed dose of the alpha-interferon (alpha-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 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 I:C-treated normal Wistar rats is attributable to a deficient alpha-IFN response. Using poly I:C 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 I:C 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 I:C-induced serum alpha-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 alpha-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum alpha-IFN and accelerates the development of diabetes in BB rats at even very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Sobel
D O
DO
Department of Pediatrics, Georgetown University School of Medicine, Washington, DC.
Ewel
C H
CH
Zeligs
B
B
Abbassi
V
V
Rossio
J
J
Bellanti
J A
JA
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB / Q000378:metabolism*; D017208:Rats, Wistar / Q000378:metabolism*; D013045:Species Specificity; D013997:Time Factors
D016898:Interferon-alpha; D011070:Poly I-C