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(Circulation. 1999;100:1102-1108.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Treatment of Experimental Viral Myocarditis With Interleukin-10
From the Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, and the Department of Internal Medicine, Utano National Hospital (H.I.), Kyoto, Japan.
Correspondence to Akira Matsumori, MD, PhD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606, Japan. E-mail amat{at}kuhp.kyoto-u.ac.jp
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.
Methods and 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 µg/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-
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.
Key Words: interleukins • myocarditis • tumor necrosis factor • nitric oxide synthase
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