This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sobel, D. O. Articles by Newsome, J. Search for Related Content PubMed PubMed Citation Articles by Sobel, D. O. Articles by Newsome, J.

 Previous Article  |  Next Article 

Clinical and Diagnostic Laboratory Immunology, 11 1997, 764-768, Vol 4, No. 6
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Gamma interferon prevents diabetes in the BB rat

DO Sobel and J Newsome
Division of Pediatric Endocrinology and Metabolism, Georgetown University Medical Center, Washington, D.C. 20007-2197, USA.

The BB rat model of human insulin-dependent diabetes mellitus (IDDM) spontaneously develops diabetes through an autoimmune process. Gamma interferon (IFN-gamma) is thought to play an important pathogenic role. This study examined if IFN-gamma administration can, paradoxically, prevent diabetes in BB rats. Diabetes-prone BB rats were initially injected intraperitoneally with murine recombinant IFN-gamma (rIFN- gamma) at doses of 0.5 x 10(4) to 40 x 10(4) U three times a week for 6 weeks beginning at 35 days of age. The effects of altering the duration of treatment (2 to 6 weeks) and the age at which injections were initiated (45 through 65 days) were also assessed. rIFN-gamma administration prevented the development of diabetes in a dose- dependent manner. The optimal treatment condition resulted in a 9.1% incidence of diabetes versus a 90% incidence in control rats. This diabetes-sparing effect was long lasting and continued to 7 months of age. A 4- to 6-week course resulted in maximal inhibition. Treatment initiated as late as 55 days of age, when insulitis is already present, was effective in preventing diabetes. Islet inflammation was dramatically lower in rIFN-gamma- versus saline-injected rats (P < 0.01). Total leukocyte count and subpopulations of peripheral mononuclear cells were unaltered by rIFN-gamma. In summary, rIFN-gamma paradoxically and potently prevents diabetes in BB rats in a dose- dependent fashion by inhibiting islet inflammation. This diabetes- sparing effect occurs even when injections are initiated after evidence of the diabetic process is already present.