{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:16:21Z","timestamp":1790889381220,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,29]]},"abstract":"<jats:p>\n                    The role of leptin was investigated in two models of T cell-mediated hepatitis: the administration of Con A or of\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    exotoxin A (PEA). In both models, leptin-deficient (\n                    <jats:italic>ob<\/jats:italic>\n                    \/\n                    <jats:italic>ob<\/jats:italic>\n                    ) mice were protected from liver damage and showed lower induction of tumor necrosis factor (TNF) \u03b1 and IL-18 compared with their lean littermates. Neutralization of TNF-\u03b1 reduced induction of IL-18 by either Con A (70% reduction) or PEA (40% reduction). Pretreatment of lean mice with either soluble TNF receptors or with an anti-IL-18 antiserum significantly reduced Con A- and PEA-induced liver damage. The simultaneous neutralization of TNF-\u03b1 and IL-18 fully protected the mice against liver toxicity. However, neutralization of either IL-18 or TNF-\u03b1 did not inhibit Con A-induced production of IFN-\u03b3. Thymus atrophy and alterations in the number of circulating lymphocytes and monocytes were observed in\n                    <jats:italic>ob<\/jats:italic>\n                    \/\n                    <jats:italic>ob<\/jats:italic>\n                    mice. Exogenous leptin replacement restored the responsiveness of\n                    <jats:italic>ob<\/jats:italic>\n                    \/\n                    <jats:italic>ob<\/jats:italic>\n                    mice to Con A and normalized their lymphocyte and monocyte populations. These results demonstrate that leptin deficiency leads to reduced production of TNF-\u03b1 and IL-18 associated with reduced T cell-mediated hepatotoxicity. In addition, both TNF-\u03b1 and IL-18 appear to be essential mediators of T cell-mediated liver injury.\n                  <\/jats:p>","DOI":"10.1073\/pnas.040561297","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"2367-2372","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":264,"title":["Leptin-deficient (\n                    <i>ob<\/i>\n                    \/\n                    <i>ob<\/i>\n                    ) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor \u03b1 and IL-18"],"prefix":"10.1073","volume":"97","author":[{"given":"Raffaella","family":"Faggioni","sequence":"first","affiliation":[{"name":"Metabolism Section, Department of Veteran Affairs Medical Center, University of California, San Francisco, CA 94121; and Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Jones-Carson","sequence":"additional","affiliation":[{"name":"Metabolism Section, Department of Veteran Affairs Medical Center, University of California, San Francisco, CA 94121; 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