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A potential mediator of muscle weakness is tumor necrosis factor (TNF)-\u03b1, a cytokine that can stimulate muscle wasting and also can induce contractile dysfunction without overt catabolism. This study addressed the latter process. Murine diaphragm and limb muscle (flexor digitorum brevis [FDB]) preparations were used to determine the relative sensitivities of these muscles to TNF-\u03b1. Intact muscle fibers were isolated from FDB and microinjected with indo-1 to measure changes in sarcoplasmic calcium regulation. We found that TNF-\u03b1 depressed tetanic force of the diaphragm and FDB to comparable degrees across a range of stimulus frequencies. In isolated muscle fibers, TNF-\u03b1 decreased tetanic force without altering tetanic calcium transients or resting calcium levels. We conclude that (1) TNF-\u03b1 compromises contractile function of diaphragm and limb muscle similarly, and (2) TNF-\u03b1 decreases force by blunting the response of muscle myofilaments to calcium activation.<\/jats:p>","DOI":"10.1164\/rccm.2202005","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T17:37:17Z","timestamp":1033493837000},"page":"479-484","source":"Crossref","is-referenced-by-count":262,"title":["Respiratory and Limb Muscle Weakness Induced by Tumor Necrosis Factor-\n                    <b>\u03b1<\/b>\n                    : Involvement of Muscle Myofilaments"],"prefix":"10.1093","volume":"166","author":[{"given":"Michael B.","family":"Reid","sequence":"first","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas; and Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"L\u00e4nnergren","sequence":"additional","affiliation":[{"name":"Baylor College of 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