{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:52:05Z","timestamp":1792525925989,"version":"4.5.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,6,1]]},"abstract":"<jats:p>Resistance to Leishmania major in mice is associated with the appearance of distinct T helper type 1 (Th1) and Th2 subsets. T cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (IFN-gamma)-producing Th1 cells. In contrast, T cells from susceptible mice are principally Th2 cells that generate interleukin 4 (IL-4). Although existing evidence is supportive of a role for IFN-gamma in the generation of Th1 cells, additional factors may be required for a protective response to be maintained. A potential candidate is IL-12, a heterodimeric cytokine produced by monocytes and B cells that has multiple effects on T and natural killer cell function, including inducing IFN-gamma production. Using an experimental leishmanial model we have observed that daily intraperitoneal administration at the time of parasite challenge of either 0.33 micrograms IL-12 (a consecutive 5 d\/wk for 5 wk) or 1.0 micrograms IL-12 per mouse (only a consecutive 5 d) caused a &amp;gt; 75% reduction in parasite burden at the site of infection, in highly susceptible BALB\/c mice. Delay of treatment by 1 wk had less of a protective effect. Concomitant with these protective effects was an increase in IFN-gamma and a decrease in IL-4 production, as measured by enzyme-linked immunosorbent assay of supernatants generated from popliteal lymph node cells stimulated with leishmanial antigen in vitro. The reduction in parasite numbers induced by IL-12 therapy was still apparent at 10 wk postinfection. In addition, we observed that the administration of a rabbit anti-recombinant murine IL-12 polyclonal antibody (200 micrograms i.p. every other day for 25 d) at the time of infection to resistant C57Bl\/6 mice exacerbated disease. These effects were accompanied by a shift in IFN-gamma production in vitro by antigen-stimulated lymph node cells indicative of a Th2-like response. These findings suggest that IL-12 has an important role in initiating a Th1 response and protective immunity.<\/jats:p>","DOI":"10.1084\/jem.177.6.1797","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1797-1802","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":455,"title":["Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response."],"prefix":"10.1084","volume":"177","author":[{"given":"J P","family":"Sypek","sequence":"first","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C L","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Mayor","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Subramanyam","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D S","family":"Sieburth","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S F","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R G","family":"Schaub","sequence":"additional","affiliation":[{"name":"Department of Preclinical Biology, Genetics Institute, Inc., Cambridge, Massachusetts 02140."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1993,6,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/177\/6\/1797\/1674395\/1797.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/177\/6\/1797\/1674395\/1797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T04:56:02Z","timestamp":1690260962000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/177\/6\/1797\/50431\/Resolution-of-cutaneous-leishmaniasis-interleukin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1993,6,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.177.6.1797","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,6,1]]}}}