Macrophage activation to kill Leishmania major: Activation of macrophages for intracellular destruction of amastigotes can be induced by both recombinant interferon-γ and non-interferon lymphokines

Macrophages treated with lymphokine (LK)-rich culture fluids from antigen- or mitogen-stimulated spleen cells or the hybridoma T cell 24/G1, or murine recombinant interferon-γ (IFN-γ) from either transfected monkey kidney cells (cos-rIFN-γ) or bacterial (E. coli) DNA (rIFN-γ) developed the capacity to kill intracellular amastigotes of Leishmania major. Removal of IFN activity from LK by neutralizing fluid phase monoclonal anti-rIFN-γ antibody, or by solid phase immunoadsorption, left residual macrophage activation factors that induced approximately 50% of the macrophage anti-leishmanial activity of untreated LK. In contrast, rIFN-γ subjected to the same antibody treatments lost all capacity to induce this macrophage effector function. These results suggest that the intracellular destruction of amastigotes is regulated by several different factors. One of these factors is clearly IFN-γ, which is pleiotropic in its effects on macrophage functions. The other non-IFN LK factors are immunochemically unrelated to IFN-γ, and may regulate macrophage microbicidal activities in a more selective manner.