Application of recombinant granulocyte-macrophage colony-stimulating factor has a detrimental effect in experimental...

The purpose of this study was to evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on BALB/c mice infected s.c. with the intracellular pathogen Leishmania major. Daily i.p. application of 1 microgram rGM-CSF for 21 days following the infection led to an aggravated course of the disease in most animals. In no case was a therapeutic effect observed. In vitro analysis revealed that the parasite burden was approx. 2- to 7-fold higher in the infected lesions, in the lymph nodes draining the infection and in the spleens of rGM-CSF-treated animals than in tissues from nontreated mice. L. major-infected macrophages obtained from chronically infected mice proliferated in the presence of rGM-CSF in vitro without gaining antiparasitic effector function. However, antiparasitic effector function increased and macrophage growth was inhibited in the presence of recombinant interferon-gamma (IFN-gamma). These data indicate that rGM-CSF-induced macrophage proliferation alone is not sufficient to overcome infections with intracellular pathogens like L. major, since simultaneous activation of macrophages by IFN-gamma is required.