INTERFERON-GAMMA INHIBITS PROLIFERATION, DIFFERENTIATION, AND CREATINE-KINASE ACTIVITY OF CULTURED HUMAN MUSCLE-CELLS .2. A POSSIBLE ROLE IN MYOSITIS

Objective. To investigate the effects of human interferon-gamma (IFN-g amma) on cultured human skeletal muscle cells. Methods. Muscle cell cu ltures were treated with various concentrations of recombinant human I FN-gamma, and muscle cell proliferation, creatine kinase synthesis and muscle cell cytotoxicity were analyzed. Results. Treatment of muscle cell cultures with IFN-gamma resulted in significant inhibition of myo blasts 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 eff ect 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-ga mma was not cytotoxic to cultured muscle cells even with very high (10 ,000 U/ml) IFN-gamma doses.Conclusion. IFN-gamma inhibits muscle cell proliferation and differentiation in vitro. These findings suggest tha t IFN-gamma, a T cell lymphokine, may inhibit muscle regeneration and the repair of injured muscle fibers in myositis.