Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment

Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder in which phagocytic leukocytes fail to generate superoxide (O-2(-)) and antimicrobial oxidants. The therapeutic validity of interferon-gamma (IFN-gamma) has been well established in CGD patients but its underlying mechanisms remain poorly understood. One probable mechanism has been suggested to be modulation of nitric oxide (NO) release from phagocytic cells. Herein, we investigated NO production from neutrophil cells in CGD patients on treatment with IFN-gamma in vivo and in vitro. We measured NO levels in sera from 19 CGD patients (group I: 7 patients treated with TMP-SMX, group II: 12 patients treated with TMP-SMX and IFN-gamma simultaneously) and healthy control individuals (8 cases). We also measured NO production from neutrophils in both patients groups as well as in control group after adding 100 U IFN-gamma in vitro. Our results showed that there was a significant difference between the groups in the NO levels of serum; patients who received IFN-gamma had significantly higher amount of NO than the other groups. Besides, NO levels increased significantly after adding 100 U IFN-gamma in vitro in three studied groups, considerably in the patients on treatment with IFN-gamma. As a brief conclusion, the effect of IFN-gamma in increasing NO production is obvious. This could be an explanation for the therapeutic effect of IFN-gamma in patients with CGD as NO acts as a bactericidal agent and plays a role in host defense mechanism instead of O-2(-). (C) 2012 Elsevier B.V. All rights reserved.