ALPHA-INTERFERON INHIBITS THE DEVELOPMENT OF DIABETES IN NOD MICE

The NOD mouse is a model of human IDDM, which is characterized by a ce ll-mediated autoimmune process resulting in spontaneous diabetes, alph a-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 diabete s and the passive transfer of diabetes in NOD mice. Spontaneous diabet es was inhibited by IFN-alpha in a dose-dependent fashion. A dose of a s 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% in cidence in control mice). Even at the termination of the experiment, n ondiabetic mice administered rIFN-alpha maintained normal glucose tole rance. Islet inflammation was 65% lower in the pancreases of rIFN-alph a mice, rIFN-alpha. administration decreased anti-islet effector cell bioactivity of spleen cells without inducing generalized immunosuppres sion. Passive transfer experiments demonstrated that the decreased ant i-isIet effector cell activity was not a direct action of rIFN-alpha o n these cells. In conclusion, rIFN-alpha potently and paradoxically pr events diabetes by indirectly decreasing anti-islet effector cell acti vity and in turn the development of insulitis without inducing general ized immunosuppression. This work, which goes against our current unde rstanding of the role of rIFN-alpha in autoimmunity, may have signific ant implications to further our understanding of the pathogenesis of I DDM and to further the development of novel modes to prevent the disea se.