Recombinant granulocyte/macrophage colony-stimulating factor activates macrophages to inhibit Trypanosoma cruzi and release hydrogen peroxide. Comparison with interferon gamma

Carl F. Nathan,D. Pihl,Paul Rodricks,K. Shanebeck,Paul J. Conlon,K. Grabstein

Published 1987 in Journal of Experimental Medicine

ABSTRACT

Recombinant granulocyte/macrophage colony-stimulating factors (rGM-CSF) of mouse and human origins activated macrophages of the homologous species to inhibit the replication of the protozoan parasite T. cruzi. Activation could be induced with 10-100 ng/ml of rMu-GM-CSF, whether it was added before or after uptake of the parasite, in either adherent or suspension cultures. However, the degree of inhibition of parasite replication after exposure to rMu-GM-CSF was not as great as after treatment with rMu-IFN-gamma, and much more rMu-GM-CSF than rMu-IFN- gamma was required to achieve an equivalent antimicrobial effect. These results were mirrored by effects of the cytokines on enhancement of H2O2-releasing capacity in resident mouse peritoneal macrophages. In the latter tests, rMu-IFN-gamma and rHu-TNF-alpha afforded a 44-51-fold enhancement over the untreated control, with a 50% effective concentration (EC50) for rMu-IFN-gamma of approximately 0.05 ng/ml. Using rMu-GM-CSF or rM-CSF, enhancement of H2O2-releasing capacity was 14-15-fold over control, with EC50s of 1 and 14 ng/ml, respectively. However, peak enhancement of macrophage H2O2-releasing capacity was seen at least 24 h earlier with rMu-GM-CSF or rHu-M-CSF than with r-Mu- IFN-gamma or rHu-TNF-alpha. Thus, rMu-GM-CSF and rHu-GM-CSF displayed clear-cut macrophage-activating activity in vitro, but rMu-GM-CSF was less potent and less effective than rMu-IFN-gamma in the tests used.

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