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Clin Immunol. 2010 Jun;135(3):401-11. doi: 10.1016/j.clim.2010.01.007. Epub 2010 Feb 18.

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

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  • 1Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 80045, USA.

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.

Copyright 2008 Elsevier Inc. All rights reserved.

PMID:
20167539
[PubMed - indexed for MEDLINE]
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