{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:00:06Z","timestamp":1789506006227,"version":"build-2803163510"},"reference-count":36,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[1996,3,1]],"date-time":"1996-03-01T00:00:00Z","timestamp":825638400000},"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":[[1996,3]]},"abstract":"<jats:p>Administration of 500 mg\/kg acetaminophen (APAP) to female B6C3F1 mice resulted in well-documented pathophysiological changes in the liver manifested as increased serum concentration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and serum sorbitol dehydrogenase), centrilobular congestion, and hepatocellular degeneration and necrosis. The role of proinflammatory cytokines, including tumor necrosis factor a (TNF-\u03b1) and interleukin 1\u03b1 (IL-1\u03b1), on the hepatotoxicity of APAP was examined at 4,8, 12, and 24 hr following APAP administration. Neutralization of TNF-\u03b1 or IL-1\u03b1 with specific antibodies partially prevented the hepatotoxic effects of APAP at the 4- and 8-hr time points. In addition, prior administration of anti-TNF-\u03b1 antibodies shortened the recovery time following APAP treatment. While IL-1 receptor antagonist (IL-1ra) had only a modest protective effect against APAP-induced liver damage, as determined by serum enzyme release, IL-1ra had no effect on the degree of hepatic congestion or necrosis at any of the time points examined. On the other hand, administration of antibodies against IL-1ra exacerbated APAP-induced liver toxicity. These results suggest that TNF-\u03b1 and IL-1\u03b1 play an important role in the degree of damage and recovery that the liver undergoes following APAP intoxication.<\/jats:p>","DOI":"10.1177\/019262339602400206","type":"journal-article","created":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T19:16:47Z","timestamp":1238613407000},"page":"181-189","source":"Crossref","is-referenced-by-count":126,"title":["Histopathology of Acetaminophen-Induced Liver Changes: Role of Interleukin 1\u03b1 and Tumor Necrosis Factor \u03b1"],"prefix":"10.1177","volume":"24","author":[{"given":"Mark E.","family":"Blazka","sequence":"first","affiliation":[{"name":"Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Elwell","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve D.","family":"Holladay","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia 24061-0442"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph E.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I.","family":"Luster","sequence":"additional","affiliation":[{"name":"Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[1996,3,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.59.070190.004031"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1992.01420010037006"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-12-917"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1125"},{"key":"atypb5","doi-asserted-by":"crossref","unstructured":"Brandes ME and Wahl SM (1994). Inflammatory cytokines: An overview. In: Xenobiotics and Inflammation, LB Schook and DL Laskin (eds). Academic Press, New York, pp. 33-70.","DOI":"10.1016\/B978-0-12-628930-5.50008-4"},{"key":"atypb6","first-page":"245","volume":"192","author":"Decker K.","year":"1990","journal-title":"J. Biochem"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.2.695.695"},{"key":"atypb8","first-page":"227","volume":"1","author":"Dinarello CA","year":"1992","journal-title":"Infect. Agents Dis"},{"key":"atypb9","first-page":"404","volume":"12","author":"Dinarello CA","year":"1991","journal-title":"Today"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(88)90072-0"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1159\/000234610"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80803-B"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-091302-2.50008-6"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)90303-1"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/34.4_ts.381"},{"key":"atypb16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0022-3565(25)29664-1","volume":"187","author":"Jollow DJ","year":"1973","journal-title":"J. Pharmacol. Exp. Therap"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1065"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5877-0_66"},{"key":"atypb19","unstructured":"Laskin DL (1992). Role of macrophages and endothelial cells in hepatotoxicity . In: Hepatocyte and Kupffer Cell Interactions, TR Billiar and RD Curran (eds). CRC Press, Boca Raton, Florida, pp. 147-168."},{"key":"atypb20","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(86)90051-7"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(86)90052-9"},{"key":"atypb22","first-page":"234","volume":"56","author":"Le J.","year":"1987","journal-title":"Lab. Invest"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840090302"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.4.931"},{"key":"atypb25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0022-3565(25)29663-X","volume":"187","author":"Mitchell JR","year":"1973","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"atypb26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-3565(25)29666-5","volume":"187","author":"Mitchell JR","year":"1973","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"atypb27","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711580113"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)90006-2"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112815"},{"key":"atypb30","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0022-3565(25)29665-3","volume":"187","author":"Potter WZ","year":"1973","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"atypb31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1981.tb01835.x"},{"key":"atypb32","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830180817"},{"key":"atypb33","unstructured":"Sokol RR and Rohlf RJ (1969). Single classification analysis of variance. In: Biometry. Freeman, San Francisco, California, pp. 204-252."},{"key":"atypb34","doi-asserted-by":"publisher","DOI":"10.1038\/346425a0"},{"key":"atypb35","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/S0140-6736(89)92394-5","volume":"8647","author":"Tracey KJ","year":"1989","journal-title":"Lancet"},{"key":"atypb36","first-page":"1622","volume":"322","author":"Van der Poll T.","year":"1990","journal-title":"J. Med"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/019262339602400206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/019262339602400206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:55:36Z","timestamp":1777654536000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/019262339602400206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1996,3]]}},"alternative-id":["10.1177\/019262339602400206"],"URL":"https:\/\/doi.org\/10.1177\/019262339602400206","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,3]]}}}