{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:55:11Z","timestamp":1791255311081,"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":[[1995,11,1]]},"abstract":"<jats:p>In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB\/c and SJL\/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB\/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.<\/jats:p>","DOI":"10.1084\/jem.182.5.1281","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1281-1290","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1067,"title":["Antibodies to interleukin 12 abrogate established experimental colitis in mice."],"prefix":"10.1084","volume":"182","author":[{"given":"M F","family":"Neurath","sequence":"first","affiliation":[{"name":"Mucosal Immunity Section, National Institutes of Health\/National Institute of Allergy and Infectious Diseases\/LCI, Bethesda, Maryland 20892-1890, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Fuss","sequence":"additional","affiliation":[{"name":"Mucosal Immunity Section, National Institutes of Health\/National Institute of Allergy and Infectious Diseases\/LCI, Bethesda, Maryland 20892-1890, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B L","family":"Kelsall","sequence":"additional","affiliation":[{"name":"Mucosal Immunity Section, National Institutes of Health\/National Institute of Allergy and Infectious Diseases\/LCI, Bethesda, Maryland 20892-1890, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"St\u00fcber","sequence":"additional","affiliation":[{"name":"Mucosal Immunity Section, National Institutes of Health\/National Institute of Allergy and Infectious Diseases\/LCI, Bethesda, Maryland 20892-1890, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Strober","sequence":"additional","affiliation":[{"name":"Mucosal Immunity Section, National Institutes of Health\/National Institute of Allergy and Infectious Diseases\/LCI, Bethesda, Maryland 20892-1890, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1995,11,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1281\/1677849\/1281.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1281\/1677849\/1281.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:00:03Z","timestamp":1690268403000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/182\/5\/1281\/25756\/Antibodies-to-interleukin-12-abrogate-established"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,11,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995,11,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.182.5.1281","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,11,1]]}}}