Interferon-gamma is unable to increase monocyte and neutrophil-mediated nonspecific cytotoxicity induced by immune complexes.

We have previously demonstrated that normal human neutrophils and monocytes triggered by immune complexes (IC) are able to destroy non-sensitized target cells through the activation of a nonspecific cytotoxic mechanism (NSC), that is dependent on the generation of reactive oxygen intermediates (IRO). In the present study, we analyze the ability of interferon-gamma (IFN-gamma) to modulate NSC. Our results indicate that, despite the ability of IFN-gamma to increase both the generation of superoxide anion and hydrogen peroxide by phagocytic cells and the expression of the high-affinity 72-kDa Fc gamma RI, it is completely unable to increase NSC mediated either by neutrophils or monocytes. These data suggest that there is no correlation between cytotoxicity and the ability of phagocytic cells to release superoxide anion and/or hydrogen peroxide. They also indicate that Fc gamma RI is not involved in the induction of NSC. To further analyze this point, we studied the ability of two monoclonal antibodies (mAb), specific for different epitopes of Fc gamma RI, to inhibit NSC. These mAb strongly inhibited ADCC mediated by untreated monocytes or IFN-gamma treated monocytes and neutrophils. On the other hand, they were completely unable to inhibit NSC mediated by untreated or IFN-gamma treated cells.