Human mononuclear cell factors suppress contractility of isolated mouse soleus muscle

Weakness in polymyositis-dermatomyositis is often greater than would be suggested by histologic evidence of fiber degeneration or necrosis. Mononuclear cell infiltration is the key pathologic feature of polymyositis-dermatomyositis, and previous studies suggest a role for cellular immunity. In this study, the effect of supernatants from mitogen-stimulated human blood mononuclear cells on contractility of isolated mouse normal soleus muscle was examined. Mononuclear cell factor-rich supernatants were generated in 5-day cultures by phytohemagglutinin P stimulation of mononuclear cells from normal volunteers. Mouse soleus muscle was mounted isometrically in a muscle bath filled with oxygenated Ringer's solution or RPMI-1640 and was stimulated electrically. In 10 individual experiments, all muscles exposed to mononuclear cell factor-rich supernatants showed a rapid and progressive decline in active force of isometric contraction; a 40% decrease in active force was observed 5 to 13 minutes (average, 8 minutes) after the addition of supernatant. The inhibitory effect was reversible on removal of mononuclear cell factor-rich supernatants. Control culture medium and supernatants from unstimulated cell cultures showed no appreciable effect on active force. The factor(s) producing suppression of muscle contractility was dialyzable and stable through several cycles of freezing and thawing. Gel chromatography (Sephadex G-25 fine) showed one active fraction corresponding to an apparent molecular weight of approximately 2000. These data indicate that factor(s) released by human mononuclear cells can directly suppress the contraction of normal skeletal muscle.