IFN-gamma produced in vivo during the first two days is critical for resolution of murine Leishmania major infections.

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.