{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:35:23Z","timestamp":1791056123400,"version":"4.1.0"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,3,3]]},"abstract":"<jats:p>Although implicated in the clinical expression of human visceral leishmaniasis, a disease-exacerbating T helper cell 2 (Th2)-associated immune response involving interleukin-4 (IL-4) and\/ or IL-10 is not readily detectable in experimental visceral infection. To overcome this obstacle to analyzing visceral Leishmania donovani in this relevant immunopathogenetic environment, we sought a model in which a Th2 response induces noncuring infection. Four initial approaches were tested primarily in BALB\/c mice which control intracellular L. donovani via an IL-12\u2013 and interferon-\u03b3 (IFN-\u03b3)\u2013dependent Th1 mechanism: (a) modifying the cytokine milieu when the parasite is first encountered (treatment with exogenous IL-4 or anti\u2013IL-12), (b) providing sustained endogenous exposure to a Th2 cytokine (infection of IL-4 transgenic mice), (c) increasing the parasite challenge inoculum, and (d) injecting heat-killed L. major promastigotes (HKLMP) to induce a cross-reactive Th2 response to live L. donovani. Only the last approach generated a functional Th2-type response that induced disease exacerbation accompanied by inhibition of tissue granuloma assembly. In HKLMP-primed BALB\/c mice, prophylaxis with anti\u2013IL-4, anti\u2013IL-10, or exogenous IL-12 (but not IFN-\u03b3) readily restored resistance. In primed mice with established visceral infection, treatment with either IL-12 or IFN-\u03b3 also successfully induced antileishmanial activity. The results in this model (a) suggest that rather than acting alone, IL-4 and IL-10 may act in concert to prevent acquisition of resistance to L. donovani, (b) reemphasize the capacity of IL-12 to reverse early Th2-related effects, and (c) demonstrate that Th1 cytokines (IL-12, IFN-\u03b3) have therapeutic action in an established systemic infection despite the presence of a disease-exacerbating Th2-type response.<\/jats:p>","DOI":"10.1084\/jem.185.5.867","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"867-874","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Behavior of \u2009Visceral <i>Leishmania donovani<\/i> in an Experimentally Induced T Helper Cell 2 (Th2)-Associated Response Model"],"prefix":"10.1084","volume":"185","author":[{"given":"Henry W.","family":"Murray","sequence":"first","affiliation":[{"name":"From the *Department of Medicine, Cornell University Medical College, New York 10021; and \u2021Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Hariprashad","sequence":"additional","affiliation":[{"name":"From the *Department of Medicine, Cornell University Medical College, New York 10021; and \u2021Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Coffman","sequence":"additional","affiliation":[{"name":"From the *Department of Medicine, Cornell University Medical College, New York 10021; and \u2021Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,3,3]]},"reference":[{"key":"2023072507160453900_B1","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1172\/JCI116372","article-title":"In vivo cytokine profiles in patients with kala-azar. 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