Gamma interferon treatment of patients with chronic granulomatous disease is associated with augmented production of nitric oxide by polymorphonuclear neutrophils

Treatment with gamma-interferon (IFN-gamma) is associated with reduced freq uency and severity of infections In chronic granulomatous disease (CGD), bu t the mechanism is unknown. Since the inducible nitric oxide (NO) synthase can be amplified by IFN-gamma in murine macrophages, for example, we hypoth esized that IFN-gamma might modulate NO release from polymorphonuclear neut rophils (PMNs) in patients with CGD, Eight patients with CGD and eight heal thy controls were studied. Each patient was given either 50 or 100 mu g of IFN-gamma per m(2) on two consecutive days. The production of NO from N-for myl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs was assessed as t he N-G-monomethyl-L-arginine-inhibitable oxidation of oxyhemoglobin to meth emoglobin in the presence of catalase and superoxide dismutase, Prior to IF N-gamma treatment, the PMNs from CGD patients produced 372 +/- 27 (mean +/- standard error of the mean) pmol of NO/10(6) PMNs at 45 min, while the con trol PMNs produced 343 +/- 44 pmol, On day 1 after IFN-gamma treatment, NO production increased to 132% +/- 25% of that for controls, and on day 3 it reached 360% +/- 37% (P < 0.001) of that for controls. On day 8, the values still remained higher, 280% +/- 78% more than the control values. Likewise , the bactericidal capacity of PMNs increased on day 3, The present data sh ow that IFN-gamma treatment of CCD patients is associated with an increased production of NO from PMNs when activated by fMLP, Since these PMNs lack t he capacity to produce superoxide anions, it is conceivable that this incre ase in NO release could be instrumental in augmenting host defense.