Effect of Therapy with Recombinant Human Interferon-γ on the Release of Nitric Oxide by Neutrophils and Mononuclear Cells from Patients with Chronic Granulomatous Disease

Abstract

The aim of this study was to investigate the effect of recombinant human interferon-γ (rHuIFN-γ) therapy on the release of nitric oxide (NO) by neutrophils (NEU) and mononuclear cells (MON) from patients with chronic granulomatous disease (CGD). Five patients with this rare disease received rHuIFN-γ (50 μg/m² of body surface, given by subcutaneous injection three times a week) for 6 months. Clinical and laboratory evaluations were performed before and after 1 and 6 months of rHuIFN-γ therapy. Nitric oxide release by NEU and MON was assessed by the ability of these cells to inhibit thrombin-induced washed platelet aggregation. The nitrite (NO₂-) and nitrate (NO₃-) levels in the supernatant of cultured NEU and MON, as well as in plasma and urine (24 h diuresis), were quantified by high-performance liquid chromatography (HPLC). Conventional immunologie tests for assessing phagocyte and lymphocyte functions and humoral immunity were also performed. Therapy with rHuIFN-γ for 6 months did not enhance NO synthesis by NEU or MON from the patients with CGD. The urinary but not plasma levels of NO₂- and NO₃- were elevated after rHuIFN-γ therapy. Phagocyte and lymphocyte functions as well as humoral immunity were not affected by rHuIFN-γ therapy. Although few patients were available for the study, we conclude that therapy with rHuIFN-γ for 6 months did not enhance the synthesis of NO by NEU and MON in CGD patients. Whether the increased excretion of NO₂- and NO₃- in the urine of CGD patients after rHUIFN-γ therapy reflects an induction of NO-synthase in cells other than leukocytes remains to be investigated.