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-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.

Deficiência da glicose-6-fosfato desidrogenase com infecções de repetição: relato de caso

“…O O 2-, ao agir como um oxidante, é reduzido para peróxido de hidrogênio (H 2 O 2 ) 6 , que é diretamente tóxico para os microorganismos 7 .…”

“…O mais usado é um exame simples e de baixo custo: o teste de redução do corante Nitrobluetetrazolium (NBT). No teste do NBT as células fagocitárias são ativadas por estímulos apropriados na presença do corante (cor amarela), que funciona como receptor de elétrons, e se reduz quando em contato com os intermediários reativos de O 2 , mudando para a cor azul, podendo ser quantificado no citoplasma dos neutrófilos, facilmente visualizados no microscópio comum 6 .…”

“…A dosagem específica do O 2-é importante, pois mostra se o defeito no metabolismo oxidativo ocorreu em sua etapa inicial 6 .…”

“…O Interferon-Gama (INF-g) ativa macrófagos in vivo e in vitro, por estimular a NADPH oxidase e aumentar a síntese de intermediários reativos de oxigênio, aumentando sua atividade microbicida em indivíduos saudáveis 6 . A terapia com Interferon Gama recombinante humano (rHuI-FN-g) foi recentemente usada em pacientes com DGC com redução do risco relativo de infeções graves em 70% dos casos 6 .…”

“…A terapia com Interferon Gama recombinante humano (rHuI-FN-g) foi recentemente usada em pacientes com DGC com redução do risco relativo de infeções graves em 70% dos casos 6 . Embora não tenha reconstituído a atividade metabólica oxidativa na maioria dos pacientes, algumas variantes de DGC -como o defeito na gp91phox e as deficiências de proteína do citosol -apresentaram melhora na resposta oxidativa 8 .…”