Increased phagocyte FcγRI expression and improved Fcγ-receptor- mediated phagocytosis after in vivo recombinant human interferon-γ treatment of normal human subjects

Abstract

Recombinant human interferon-γ (rhIFN-2c) decreases the frequency of serious infections in patients with chronic granulomatous disease (CGD) through an unknown mechanism. To test the hypothesis that it exerts a beneficial effect by enhancing clearance of microbes from the bloodstream and tissues, normal human subjects were treated in vivo with rhIFN-γ. Phagocyte opsonic receptor expression, serum opsonin levels, and phagocytosis of bacteria were then measured. A 4.7-fold increase in neutrophil expression of the high-affinity Fcγ-receptor (FcγRI) was observed that peaked 48 hours after the initiation of rhIFN-γ treatment (P < .05). Monocyte expression of FcγRI, FcyRII, FcγRIII, CD11a, CD11b, CD18, and HLA-DR also significantly increased with peak expression at 48 hours. Phagocytosis by neutrophils of killed Staphylococcus aureus opsonized with heat-inactivated pooled human serum significantly improved after rhIFN-γ treatment (P < .05) and correlated with FcγRI expression by neutrophils (r = .8, P < .001). This increase in ingestion could be inhibited by anti-FcγRI monoclonal antibodies. Levels of the serum opsonin lipopolysaccharide-binding protein also significantly increased after in vivo rhIFN-γ (P < .05). These results suggest that the protective effect of rhIFN-γ in patients with CGD may involve improved microbial clearance. Moreover, improved phagocyte trafficking may occur secondary to increased expression of monocyte β2- integrins. Because these IFN-γ-related improvements in host defense were seen in normal hosts, rhIFN-γ, may have broader applications in the treatment of various disorders of immunity in addition to its demonstrated efficacy in CGD.