INCREASED PHAGOCYTE FC-GAMMA-RI EXPRESSION AND IMPROVED FC-GAMMA-RECEPTOR-MEDIATED PHAGOCYTOSIS AFTER IN-VIVO RECOMBINANT HUMAN INTERFERON-GAMMA TREATMENT OF NORMAL HUMAN-SUBJECTS

Recombinant human interferon-gamma (rhIFN-gamma) decreases the frequen cy of serious infections in patients with chronic granulomatous diseas e (CGD) through an unknown mechanism. To test the hypothesis that it e xerts a beneficial effect by enhancing clearance of microbes from the bloodstream and tissues, normal human subjects were treated in vivo wi th rhIFN-gamma. Phagocyte opsonic receptor expression, serum opsonin l evels, and phagocytosis of bacteria were then measured. A 4.7-fold inc rease in neutrophil expression of the high-affinity Fc gamma-receptor (Fc gamma RI) was observed that peaked 48 hours after the initiation o f rhIFN-gamma treatment (P < .05). Monocyte expression of Fc gamma RI, Fc gamma RII, Fc gamma RIII, CD11a, CD11b, CD18, and HLA-DR also sign ificantly increased with peak expression at 48 hours. Phagocytosis by neutrophils of killed Staphylococcus aureus opsonized with heat-inacti vated pooled human serum significantly improved after rhIFN-gamma trea tment (P < .05) and correlated with Fc gamma RI expression by neutroph ils (r = .8, P < .001). This increase in ingestion could be inhibited by anti-Fc gamma RI monoclonal antibodies. Levels of the serum opsonin lipopolysaccharide-binding protein also significantly increased after in vivo rhIFN-gamma (P < .05). These results suggest that the protect ive effect of rhIFN-gamma in patients with CGD may involve improved mi crobial clearance. Moreover, improved phagocyte trafficking may occur secondary to increased expression of monocyte beta(2)-integrins. Becau se these IFN-gamma-related improvements in host defense were seen in n ormal hosts, rhIFN-gamma may have broader applications in the treatmen t of various disorders of immunity in addition to its demonstrated eff icacy in CGD. (C) 1997 by The American Society of Hematology.