Brief dexamethasone treatment during acute infection prevents virus-induced autoimmune diabetes

Abstract

We used the LEW1.WR1 rat to test the hypothesis that Kilham rat virus-induced innate immune activation is involved in the mechanism of autoimmune diabetes. Animals were treated with dexamethasone, an anti-inflammatory glucocorticoid, beginning on the day of infection. Administering dexamethasone on five consecutive days completely blocked the disease. Strikingly, a single dose of dexamethasone was sufficient to prevent islet destruction. Dexamethasone downmodulated inflammation and restored normal ratios between CD8(+) and CD4(+)CD25(+)Foxp3(+) cells in the spleen. Finally, dexamethasone therapy lowered the frequency of splenic anti-virus CD8(+) T cells, but did not interfere with the ability of the host to generate anti-KRV antibodies and eliminate the virus from the spleen. Our data demonstrate a strong association between early virus-induced proinflammatory responses and islet destruction and raise the possibility that targeting innate immune pathways in the early stages of diabetes may be a useful strategy for disease prevention.