title: Effect of therapy with recombinant human interferon-gamma 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-gamma (rHuIFN-gamma) 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-gamma (50 micrograms/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-gamma 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 immunologic tests for assessing phagocyte and lymphocyte functions and humoral immunity were also performed. Therapy 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 levels of NO2- and NO3- were elevated after rHuIFN-gamma therapy. Phagocyte and lymphocyte functions as well as humoral immunity were not affected by rHuIFN-gamma therapy. Although few patients were available for the 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. Whether the increased excretion of NO2- and NO3- in the urine of CGD patients after rHUIFN-gamma therapy reflects an induction of NO-synthase in cells other than leukocytes remains to be investigated.
authors.affiliation: Department of Pediatrics, State University of Campinas, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Condino-neto
authors.forename: M N
authors.initials: MN
authors.lastname: Muscará
authors.forename: R
authors.initials: R
authors.lastname: Bellinati-Pires
authors.forename: M M
authors.initials: MM
authors.lastname: Carneiro-Sampaio
authors.forename: A C
authors.initials: AC
authors.lastname: Brandão
authors.forename: A S
authors.initials: AS
authors.lastname: Grumach
authors.forename: G
authors.initials: G
authors.lastname: De Nucci
mesh_terms: D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D001770:Blood Bactericidal Activity / Q000187:drug effects; D016516:CD4-CD8 Ratio; D016022:Case-Control Studies; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood / Q000652:urine; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins
chemical_list: D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma