Exercise is known to promote cytokine production, which can result in inflammation, and/or growth and repair of skeletal muscle. The cellular source of cytokines produced as a result of exercise, however is largely unknown. PURPOSE: To determine if cultured differentiated skeletal muscle cells (myotubes) release cytokines under a control condition (CT) and/or after varying degrees of mechanical strain (ST1, ST2, ST3, ST4). METHODS: Human myotubes were mechanically strained using a Flexercell Tension System. Media from CT and strained myotubes were assayed for cytokine concentrations with a cytokine multiplex kit (Linco) using Luminex technology. Myotube injury was assessed by measuring lactate dehydrogenase release. RESULTS: ST2, ST3, and ST4 were increasingly injurious to myotubes. The maj ority of cytokines (18 out of the 22) were detected in CT media, although some were detected at very low levels. IL-8, MCP-1, G-CSF, IL-6, and GM-CSF were elevated above CT after the most injurious strain (ST4). In addition, IL-8 and MCP-1 were sensitive to the degree of strain with increased concentrations detected with progressive grades of strain. CONCLUSION: Preliminary results demonstrate that skeletal myotubes constitutively secrete a low level of multiple cytokines; whereas injurious mechanical strain induces greater release of a small number of cytokines. Cytokine release from skeletal muscle cells may promote inflammation, angiogenesis and/or influence the growth and/or repair of skeletal muscle after exercise. Supported by an ACSM foundation research grant.