Inhibitory effects of interferon-γ on myocardial hypertrophy

Prostaglandin F2(alpha) (PGF2(alpha).) plays an important role in pathologic cardiac growth. After testing several immune cytokines, we found that interferon-gamma (IFN-gamma) inhibited responsiveness of adult myocytes to PGF2(alpha). The present study was designed to test the hypothesis that IFN-gamma inhibits cardiac hypertrophy induced by PGF2(alpha). Incubation of cultured adult rat cardiac myocytes with PGF2(alpha). caused cell spreading, which was inhibited by IFN-gamma. The inhibitory effect was not affected by nitric oxide (NO) synthase inhibitors. In addition, administration of fluprostenol, a more selective agonist at the PGF2(alpha). receptor, induced cardiac hypertrophy in rats. Chronic treatment with IFN-gamma inhibited this myocardial growth, and the inhibitory effect of IFN-gamma was not accompanied by an increase in myocardial NO synthase gene expression. Further, abdominal aortic constriction resulted in a substantial increase in heart, ventricular and left ventricular weights to BW ratio that was significantly attenuated by treatment with IFN-gamma. The results demonstrate that IFN-gamma inhibits the in vitro and in vivo effects of PGF2(alpha), on cardiac hypertrophy, and that the mechanism of action is likely independent of NO production. IFN-gamma also attenuated cardiac hypertrophy induced by pressure overload, suggesting that PGF2(alpha). plays a role in the pathogeneses of this severe type of cardiac hypertrophy. C 2005 Elsevier Ltd. All rights reserved.