Interferon-gamma inhibits proliferation, differentiation, and creatine kinase activity of cultured human muscle cells. II. A possible role in myositis.

Abstract

To investigate the effects of human interferon-gamma (IFN-gamma) on cultured human skeletal muscle cells. Muscle cell cultures were treated with various concentrations of recombinant human IFN-gamma, and muscle cell proliferation, creatine kinase synthesis and muscle cell cytotoxicity were analyzed. Treatment of muscle cell cultures with IFN-gamma resulted in significant inhibition of myoblasts proliferation, growth, and fusion into multinucleated myotubes. IFN-gamma inhibited creatine kinase synthesis if applied before, but not after, the myoblasts begin to differentiate into myotubes. The effect of IFN-gamma was dose dependent and observed at a concentration of IFN-gamma as low as 10 U/ml. Despite these cytostatic effects, IFN-gamma was not cytotoxic to cultured muscle cells even with very high (10,000 U/ml) IFN-gamma doses. IFN-gamma inhibits muscle cell proliferation and differentiation in vitro. These findings suggest that IFN-gamma, a T cell lymphokine, may inhibit muscle regeneration and the repair of injured muscle fibers in myositis.