Interferon-gamma inhibits proliferation, differentiation, and creatine kinase activity of cultured human muscle cells. II. A possible role in myositis.
OBJECTIVE
To investigate the effects of human interferon-gamma (IFN-gamma) on cultured human skeletal muscle cells.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kalovidouris
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Rheumatology Section, Richard L. Roudebush Veterans Affairs Medical Center, Indiana University, School of Medicine, Indianapolis 46202.
Plotkin
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Graesser
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D
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009220:Myositis / Q000201:enzymology* / Q000473:pathology*; D009994:Osmolar Concentration
D007371:Interferon-gamma; D003402:Creatine Kinase