{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:19:51Z","timestamp":1791987591912,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172149"],"award-info":[{"award-number":["82172149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970469"],"award-info":[{"award-number":["81970469"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory cytokine interleukin\u20106 (IL\u20106) plays a pivotal role in skeletal muscle degradation after intra\u2010abdominal sepsis (IAS), with mechanism remained to be elucidated. Indoleamine 2,3\u2010dioxygenase 1 (IDO\u20101), a key enzyme in converting tryptophan into kynurenine, could be activated by IL\u20106, and kynurenine has been shown to be involved in muscle degradation. We hypothesized that IL\u20106 could promote muscle degradation via tryptophan\u2013IDO\u20101\u2013kynurenine pathway in IAS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum and rectus abdominis (RA) were obtained from IAS or non\u2010IAS patients. Mouse model of IAS\u2010induced muscle wasting was generated by caecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection. IL\u20106 signalling was blocked by anti\u2010mouse IL\u20106 antibody (IL\u20106\u2010AB), and the IDO\u20101 pathway was blocked by navoximod. To elucidate the role of kynurenine in muscle mass and physiology, kynurenine was administered to IAS mice treated with IL\u20106\u2010AB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to non\u2010IAS patients, kynurenine levels in serum (+2.30\u2010fold vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and RA (+3.11\u2010fold vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) were elevated, whereas tryptophan levels in serum (\u221253.65% vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and RA (\u221261.39% vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) were decreased. Serum IL\u20106 level of the IAS group was significantly higher compared to non\u2010IAS patients (+5.82\u2010fold vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), and muscle cross\u2010sectional area (MCSA) was markedly reduced compared to non\u2010IAS patients (\u221227.73% vs. non\u2010IAS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). In animal experiments, IDO\u20101 expression was up\u2010regulated in the small intestine, colon and blood for CLP or LPS\u2010treated mice, and there was correlation (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.66, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) between serum and muscle kynurenine concentrations. Navoximod significantly mitigated IAS\u2010induced skeletal muscle loss according to MCSA analysis (+22.94% vs. CLP, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05; +23.71% vs. LPS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and increased the phosphorylated AKT (+2.15\u2010fold vs. CLP, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01; +3.44\u2010fold vs. LPS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and myosin heavy chain (+3.64\u2010fold vs. CLP, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01; +2.13\u2010fold vs. LPS, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) protein expression in myocytes. In the presence of anti\u2010IL\u20106 antibody, a significantly decreased IDO\u20101 expression was observed in the small intestine, colon and blood in CLP or LPS mice (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), whereas the decrease of MCSA was alleviated (+37.43% vs. CLP\u00a0+\u00a0IgG, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001; +30.72% vs. LPS\u00a0+\u00a0IgG, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). In contrast, additional supplementation of kynurenine decreased the MCSA in septic mice treated with IL\u20106\u2010AB (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provided novel insights into the tryptophan\u2013IDO\u20101\u2013kynurenine\u2010dependent mechanisms that underlie inflammatory cytokine\u2010induced skeletal muscle catabolism during intra\u2010abdominal sepsis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13193","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T08:26:22Z","timestamp":1678177582000},"page":"1046-1059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Interleukin\u20106 promotes skeletal muscle catabolism by activating tryptophan\u2013indoleamine 2,3\u2010dioxygenase 1\u2013kynurenine pathway during intra\u2010abdominal sepsis"],"prefix":"10.1002","volume":"14","author":[{"given":"Tingbin","family":"Xie","sequence":"first","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College  Jiangsu, P.R. 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