Inhibitory effects of interferon-γ on myocardial hypertrophy

Prostaglandin F2α (PGF2α) plays an important role in pathologic cardiac growth. After testing several immune cytokines, we found that interferon-γ (IFN-γ) inhibited responsiveness of adult myocytes to PGF2α. The present study was designed to test the hypothesis that IFN-γ inhibits cardiac hypertrophy induced by PGF2α. Incubation of cultured adult rat cardiac myocytes with PGF2α caused cell spreading, which was inhibited by IFN-γ. The inhibitory effect was not affected by nitric oxide (NO) synthase inhibitors. In addition, administration of fluprostenol, a more selective agonist at the PGF2α receptor, induced cardiac hypertrophy in rats. Chronic treatment with IFN-γ inhibited this myocardial growth, and the inhibitory effect of IFN-γ 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-γ. The results demonstrate that IFN-γ inhibits the in vitro and in vivo effects of PGF2α on cardiac hypertrophy, and that the mechanism of action is likely independent of NO production. IFN-γ also attenuated cardiac hypertrophy induced by pressure overload, suggesting that PGF2α plays a role in the pathogeneses of this severe type of cardiac hypertrophy.