GAMMA-INTERFERON PREVENTS DIABETES IN THE BB RAT

The BB rat model of human insulin-dependent diabetes mellitus (IDDM) s pontaneously develops diabetes through an autoimmune process. Gamma in terferon (IFN-gamma) is thought to play an important pathogenic role, This study examined if IFN-gamma administration can, paradoxically, pr event diabetes in BE rats. Diabetes-prone BE rats were initially injec ted intraperitoneally with murine recombinant IFN-gamma (rIFN-gamma) a t 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 t reatment (2 to 6 weeks) and the age at which injections were initiated (45 through 65 days) were also assessed. rIFN-gamma administration pr evented the development of diabetes in a dose-dependent manner, The op timal treatment condition resulted in a 9.1% incidence of diabetes ver sus 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 r esulted 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-ver sus saline-injected rats (P < 0.01), Total leukocyte count and subpopu lations of peripheral mononuclear cells were unaltered by rIFN-gamma, In summary, rIFN-gamma paradoxically and potently prevents diabetes in BE rats in a dose dependent fashion by inhibiting islet inflammation, This diabetes-sparing effect occurs even when injections are initiate d after evidence of the diabetic process is already present.