{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T11:06:48Z","timestamp":1769339208410,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Histologic studies of the muscles suggest that cytokines are involved in inflammatory myopathy. The therapeutic effects of cytokine blockade are controversial, with anecdotal reports of clinical efficacy. The aim of this study was to discern the significance of interleukin\u20101 (IL\u20101) and tumor necrosis factor \u03b1 (TNF\u03b1) as therapeutic targets in polymyositis (PM) by studying their involvement and the effects of their blockade in C protein\u2013induced myositis (CIM), a murine model of PM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice were immunized with recombinant skeletal C protein fragments to induce CIM. The expression of IL\u20101 and TNF\u03b1 in the muscles of mice with CIM was detected using immunohistochemical and real\u2010time polymerase chain reaction analyses. After the onset of myositis, the mice with CIM were treated with recombinant IL\u20101 receptor antagonist (IL\u20101Ra), anti\u2013IL\u20101R monoclonal antibody, recombinant TNF receptor (p75)\u2013fusion protein (TNFR\u2010Fc), or anti\u2010TNF\u03b1 monoclonal antibody. The muscles were examined histologically for the severity of myositis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u20101\u03b1\u2013 and TNF\u03b1\u2010positive macrophages were observed in the muscle tissue of mice with CIM as early as 7 days after immunization. IL\u20101\u03b1, IL\u20101\u03b2, and TNF\u03b1 expression in the muscles increased as the severity of myositis peaked, at both the messenger RNA and protein levels. Continuous subcutaneous delivery of IL\u20101Ra resulted in suppression of established CIM. Intermittent delivery (1\u2010day intervals) of anti\u2013IL\u20101R monoclonal antibody suppressed myositis, while intermittent delivery of IL\u20101Ra did not suppress myositis. Treatment with anti\u2010TNF\u03b1 monoclonal antibody and with TNFR\u2010Fc also reduced the severity of CIM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IL\u20101 and TNF blockade ameliorated CIM after disease onset and should potentially be a new strategy for the treatment of inflammatory myopathy. As IL\u20101 blockade, treatment with anti\u2013IL\u20101R monoclonal antibody appeared more feasible than the other approaches.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34465","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T01:27:36Z","timestamp":1330997256000},"page":"2655-2662","source":"Crossref","is-referenced-by-count":26,"title":["Interleukin\u20101 and tumor necrosis factor \u03b1 blockade treatment of experimental polymyositis in 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