title: IFN-gamma produced in vivo during the first two days is critical for resolution of murine Leishmania major infections.
abstract: Resolution of murine infection with Leishmania major is dependent upon the presence of IFN-gamma during the first week of infection. To more precisely determine the period during which IFN-gamma is critical, we infected footpads of resistant C3H/HeN mice with amastigotes of L. major and treated these mice with neutralizing monoclonal Ab (MAb) specific for IFN-gamma on successive days. Mice treated with anti-IFN-gamma MAb on or before day 2 had significantly enlarged lesions, and increased parasites in lesions, compared with mice treated with an isotype control MAb. In contrast, mice treated with anti-IFN-gamma MAb on day 3 or later resolved their lesions and had no parasites at the inoculation site. Related experiments obtained with a neutralizing MAb specific for TNF-alpha demonstrated the critical role TNF-alpha plays in resolution of Leishmania infection. Thus, IFN-gamma and TNF-alpha were both critical for resolution of infection with L. major, with IFN-gamma's role limited to the first 2 days.
authors.affiliation: Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: D A
authors.initials: DA
authors.lastname: Leiby
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: C A
authors.initials: CA
authors.lastname: Nacy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D007371:Interferon-gamma