| Interferon-beta has previously been shown to decrease the development of pathological fibrosis in various profibrotic diseases. Viral myocarditis leading to dilated cardiomyopathy is a condition with high mortality associated with myocyte destruction and fibrosis. To determine if IFN-beta tan attenuate fibrosis in viral myocarditis, and have therapeutic value, we performed experiments whereby coxsackievirus B3 (CVB3) infected mite were randomized to treatment with IFN-beta, or placebo control. We found that IFN-beta administration ameliorated the development of fibrosis, as quantitated by picrosirius red staining, in infected mite at day 7 (15.3% +/- 1.7% vs. 5.8% +/- 0.5%, percent of fibrotic area from baseline, mean +/- SEM, p<0.05) and day 14 (13.4% +/- 1.6% vs. 4.2% +/- 0.4%, percent of fibrotic area from baseline, p<0.05). Associated with the decrease in fibrosis was the down regulation of thrombospondin (TSP)-1/2 (0.386 +/- 0.034 untreated vs. 0.192 +/- 0.049 treated, p<0.05, expressed in arbitrary units) and connective tissue growth factor (CTGF) (110.33 +/- 8.41 untreated vs. 73.98 +/- 1.36 treated, p<0.05, expressed in arbitrary units) in treated mite. These results suggest that IFN-beta is regulating the TGFbeta1 signaling pathway by downregulating CTGF, the key molecule setting up positive feedback, to attenuate the development of fibrosis in murine CVB3-induced myocarditis. |
