Treatment of experimental viral myocarditis with interleukin-10.
BACKGROUND
The T helper cell type 2-associated cytokine interleukin (IL)-10 has a variety of immunomodulatory properties. However, the effects of the cytokine on viral myocarditis remain unclear.


RESULTS
We studied the effects of recombinant human IL-10 (rhIL-10) fully active on mouse cells in a murine experimental model of acute viral myocarditis caused by the encephalomyocarditis virus (EMCV). Four-week-old DBA/2 mice were inoculated with EMCV (day 0). rhIL-10 (10 microg/mouse) was administered once daily, starting on day 0, and control mice received vehicle only. Survival rates were determined on day 14. Myocardial histopathology, cytokine levels in the heart by ELISA assay, and myocardial virus concentration were examined on day 6, and the expression levels of myocardial inducible nitric oxide synthase (iNOS) mRNA were measured by competitive polymerase chain reaction. The 14-day survival in mice treated with rhIL-10 was significantly higher (80%) than in the control group (30%, n=10 in each, P<0.05). rhIL-10 treatment significantly attenuated myocardial lesions and suppressed tumor necrosis factor-alpha and IL-2 in the heart. rhIL-10 treatment had little effect on myocardial virus concentration. The expression levels of myocardial iNOS mRNA were significantly decreased in the group treated with rhIL-10 (8.6+/-4.7 amol/mg total RNA in treated versus 26.5+/-7.1 amol/mg total RNA in control mice, P<0.05).


CONCLUSIONS
These findings provide new insights into the in vivo effects of IL-10 on viral infection and suggest a therapeutic effect of IL-10 on viral myocarditis.
Nishio
R
R
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Matsumori
A
A
Shioi
T
T
Ishida
H
H
Sasayama
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018188:Cardiovirus Infections; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004686:Encephalomyocarditis virus; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000188:drug therapy* / Q000821:virology*; D009206:Myocardium / Q000378:metabolism; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016753:Interleukin-10