Alpha-interferon inhibits the development of diabetes in NOD mice.
The NOD mouse is a model of human IDDM, which is characterized by a cell-mediated autoimmune process resulting in spontaneous diabetes. Alpha-interferon (IFN-alpha) is thought to play a pathogenic role in this autoimmune process. We report that recombinant alpha-interferon (rIFN-alpha) administration decreases the development of spontaneous diabetes and the passive transfer of diabetes in NOD mice. Spontaneous diabetes was inhibited by IFN-alpha in a dose-dependent fashion. A dose of as little as 20 x 10(3) U inhibited diabetes development, while a dose of 100 x 10(3) U potently prevented diabetes (14% incidence vs. 70% incidence in control mice). Even at the termination of the experiment, nondiabetic mice administered rIFN-alpha maintained normal glucose tolerance. Islet inflammation was 65% lower in the pancreases of rIFN-alpha mice. rIFN-alpha administration decreased anti-islet effector cell bioactivity of spleen cells without inducing generalized immunosuppression. Passive transfer experiments demonstrated that the decreased anti-islet effector cell activity was not a direct action of rIFN-alpha on these cells. In conclusion, rIFN-alpha potently and paradoxically prevents diabetes by indirectly decreasing anti-islet effector cell activity and in turn the development of insulitis without inducing generalized immunosuppression. This work, which goes against our current understanding of the role of rIFN-alpha in autoimmunity, may have significant implications to further our understanding of the pathogenesis of IDDM and to further the development of novel modes to prevent the disease.
Sobel
D O
DO
Division of Pediatric Endocrinology and Metabolism, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Ahvazi
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D003208:Concanavalin A