{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:20:07Z","timestamp":1789780807790,"version":"4.0.1"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T00:00:00Z","timestamp":1240531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>Cycloheximide (CHX)-induced liver injury in rats has been characterized by hepatocellular apoptosis and necrosis. We previously reported that Kupffer cell inactivation causes a reduction of IL-10 production, resulting in the exacerbation of CHX-induced liver injury. In this study, we directly evaluate the role of IL-10 in liver injury by a pretreatment with anti-IL-10 neutralizing antibody (IL-10Ab). Rats were given goat IgG or IL-10Ab before being treated with CHX (CHX group or IL-10Ab\/CHX group). In the CHX group, the CHX treatment markedly induced hepatic mRNA and serum protein levels of IL-10. The up-regulation of IL-10 was significantly suppressed in the IL-10Ab\/CHX group. Blocking IL-10 in the IL-10Ab\/ CHX group led to greater increases in hepatic mRNA and serum levels of proinflammatory cytokines, such as TNF-\u03b1 and IL-6. The IL-10Ab\/CHX group developed more severe hepatocellular apoptosis, neutrophil transmigration, and necrotic change of hepatocytes compared with the CHX group. The caspase activities and mRNA levels of Cc120, LOX-1, and E-selectin in the livers were significantly higher in the IL-10Ab\/CHX group than the CHX group. These results demonstrate that IL-10 plays an important role in counteracting the effect of proinflammatory cytokines, such as a TNF signaling cascade, and in attenuating the CHX-induced liver injury.<\/jats:p>","DOI":"10.1177\/0192623309336153","type":"journal-article","created":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T21:27:39Z","timestamp":1240608459000},"page":"536-546","source":"Crossref","is-referenced-by-count":8,"title":["Neutralization of IL-10 Exacerbates Cycloheximide-Induced Hepatocellular Apoptosis and Necrosis"],"prefix":"10.1177","volume":"37","author":[{"given":"Kazuyoshi","family":"Kumagai","sequence":"first","affiliation":[{"name":"Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Fukuroi, Shizuoka 437-0065, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Ito","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Fukuroi, Shizuoka 437-0065, 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