{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:12:41Z","timestamp":1791094361654,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,5,1]]},"abstract":"<jats:p>This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB\/c mice were given a single intravenous injection of concanavalin A (Con A) (&amp;gt; or = 0.3 mg\/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB\/c nu\/nu mice or BALB\/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.<\/jats:p>","DOI":"10.1084\/jem.179.5.1529","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1529-1537","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":410,"title":["T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6."],"prefix":"10.1084","volume":"179","author":[{"given":"H","family":"Mizuhara","sequence":"first","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"O'Neill","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Seki","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Ogawa","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Kusunoki","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Otsuka","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Satoh","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Niwa","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Senoh","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1994,5,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/5\/1529\/1675682\/1529.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/5\/1529\/1675682\/1529.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:00:08Z","timestamp":1690264808000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/5\/1529\/25092\/T-cell-activation-associated-hepatic-injury"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1994,5,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.5.1529","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,5,1]]}}}