EFFECT OF THERAPY WITH RECOMBINANT HUMAN INTERFERON-GAMMA ON THE RELEASE OF NITRIC-OXIDE BY NEUTROPHILS AND MONONUCLEAR-CELLS FROM PATIENTSWITH CHRONIC GRANULOMATOUS-DISEASE

The aim of this study was to investigate the effect of recombinant hum an interferon-gamma (rHuIFN-gamma) therapy on the release of nitric ox ide (NO) by neutrophils (NEU) and mononuclear cells (MON) from patient s with chronic granulomatous disease (CGD), Five patients with this ra re disease received rHuIFN-gamma (50 mu g/m(2) of body surface, given by subcutaneous injection three times a week) for 6 months. Clinical a nd laboratory evaluations were performed before and after 1 and 6 mont hs of rHuIFN-gamma therapy, Nitric oxide release by NEU and MON was as sessed by the ability of these cells to inhibit thrombin-induced washe d platelet aggregation, The nitrite (NO2-) and nitrate (NO3-) levels i n the supernatant of cultured NEU and MON, as well as in plasma and ur ine (24 h diuresis), were quantified by high-performance liquid chroma tography (HPLC), Conventional immunologic tests for assessing phagocyt e and lymphocyte functions and humoral immunity were also performed, T herapy with rHuIFN-gamma for 6 months did not enhance NO synthesis by NEU or MON from the patients with CGD, The urinary but not plasma leve ls of NO2- and NO3- were elevated after rHuIFN-gamma therapy, Phagocyt e and lymphocyte functions as well as humoral immunity were not affect ed by rHuIFN-gamma therapy, Although few patients were available for t he study, we conclude that therapy with rHuIFN-gamma for 6 months did not enhance the synthesis of NO by NEU and MON in CGD patients. Whethe r the increased excretion of NO2- and NO3- in the urine of CGD patient s after rHUIFN-gamma therapy reflects an induction of NO-synthase in c ells other than leukocytes remains to be investigated.