Brief dexamethasone treatment during acute infection prevents virus-induced autoimmune diabetes.
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.
Londono
Pilar
P
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 80045, USA.
Komura
Akiko
A
Hara
Naoko
N
Zipris
Danny
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002469:Cell Separation; D003907:Dexamethasone / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology; D010322:Parvoviridae Infections / Q000150:complications; D017992:Parvovirus; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000914:Antibodies, Viral; D003907:Dexamethasone