Recombinant Interferon Gamma Augments Phagocyte Superoxide Production and X-Chronic Granulomatous Disease Gene Expression in X-Linked Variant Chronic Granulomatous Disease

We examined the potential of interferon gamma (IFN-gamma) to ameliorate the physiologic defect of chronic granulomatous disease (CGD) by studying its effects on CGD phagocyte su-peroxide generation, NADPH oxidase kinetics, cytochrome b559 content, and expression of X-CGD (the gene for the X-linked disease). Granulocytes and macrophages from three pa-tients in two kindreds with "variant " X-linked CGD (i.e., with very low, but detectable, baseline superoxide-generating activ-ity) responded to IFN-gamma with enhanced nitroblue tetra-zolium reduction and two- to eightfold increases in superoxide generation. IFN-gamma did not augment the respiratory burst activity of phagocytes from patients with "classic " CGD (i.e., no detectable baseline superoxide generation) or autosomal variant CGD. Incubation of a responding patient's granulo-cytes with IFN-gamma nearly doubled the maximal velocity for the NADPH oxidase, but did not change its abnormal Mi-chaelis constant. Although the interferon-treated CGD granu-locytes produced superoxide at a rate 40 % of normal, the cy-tochrome b spectrum remained undetectable. IFN-gamma treatment of cultured monocytes from an IFN-gamma-respon-sive CGD patient increased the steady state level of RNA transcripts from the X-CGD gene from barely detectable up to- 5 % of normal