Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by early onset of recurrent and severe
infections. The molecular defects causing CGD are heterogeneous and lead to absence, low expression, or malfunctioning of one of the phagocyte
NADPH oxidase components. It is known that mutations leading to CGD reside within the genes encoding four essential components of the
oxidase designated as gp91-phox (phagocyte
oxidase), p22-phox, p47-phox and
p67-phox. gp91- together with p22-phox form the membrane
cytochrome b(558) and play an essential role in the transfer of electrons following assembly of the active
oxidase with the cytoplasmic p47- and
p67-phox components. In hematopoietic cells, CYBB expression (the gene encoding gp91-
phox) is limited to the granulocyte and monocyte/macrophage lineages during the process of terminal differentiation. CYBB is responsive to a number of inflammatory
cytokines, especially
interferon-gamma (IFN-gamma) and
tumor necrosis factor alpha (
TNF-alpha).
Cytokines have been also studied for activation of phagocytes respiratory burst. IFN-gamma stimulates
superoxide release and is a prophylactic agent for CGD. It has been shown in vitro and in vivo to correct at least in part alterations of the oxidative metabolism, and to improve their microbicidal function. It has demonstrated clinical benefit in the majority of patients with CGD, reducing the relative risk of severe
infections in 70%. In this study, we review mechanisms showing that IFN-gamma improves the splicing efficiency of CYBB gene transcripts in a particular group of CGD patients. The present article is an informative review of recent patents related to the use of
interferon gamma therapy in
chronic granulomatous disease.