RECOMBINANT GRANULOCYTE/MACROPHAGE COLONY-STIMULATING FACTOR ACTIVATES MACROPHAGES TO INHIBIT TRYPANOSOMA CRUZI AND RELEASE HYDROGEN PEROXIDE Comparison with Interferon y BY STEVEN G. REED,* CARL F. NATHAN,* DEANNA L. PIHL,*

Trypanosoma cruzi, the etiologic agent of Chagas' disease, replicates in the cytoplasm of mononuclear phagocytes . In vitro, factors released by antigenor mitogen-stimulated T lymphocytes can activate macrophages to inhibit the growth of this protozoan (l, 2) . Interferon y (IFN--y) appears to be one of the principal lymphokines that can activate macrophages for resistance to a wide variety of intracellular microbial pathogens (reviewed in 3), including T. cruzi (4, 5) . However, there are additional macrophage-activation factors (6-10), some of which may have a narrower spectrum of activity (7, 8) . Defined cytokines with ability to enhance macrophage antimicrobial activity include recombinant tumor necrosis factor a (rHu-TNF-a) (tested with T. cruzi [8]) and partially purified murine granulocyte/macrophage colony-stimulating factor (Mu-GM-CSF)' (tested with leishmania [9]) . In addition, a twoto threefold stimulation of macrophage respiratory burst capacity was reported with partially purified macrophage colony-stimulating factor (M-CSF) (10) . Studies with recombinant cytokines are needed to confirm macrophage activation by CSFs, characterize their spectrum of activity, establish their potency, and explore their mechanisms of action . The cloning and expression (11), and purification of murine GM-CSF now permit the study of its macrophage-activating potential using a well-characterized population of tissue macrophages, those from the mouse peritoneal cavity . Such studies are reported below, along with comparative experiments using rMu-IFN7 and experiments using human monocytes and macrophages stimulated with