Interferon-gamma in the treatment of the chronic granulomatous diseases of childhood.
The bactericidal activity of phagocytic cells depends largely on the production of highly reactive metabolites from the metabolism of oxygen. A lesion anywhere in the biochemical pathway of hydrogen peroxide production has the potential to cause chronic granulomatous disease (CGD). Recent findings have shown that CGD results from distinct abnormalities in the NADPH oxidase system, which includes the membrane-associated proteins, NADPH oxidase, cytochrome b-558, and several cytosolic proteins. Specific genetic markers have been identified for the most common biochemical variants of CGD. Pharmacologic alteration of phagocyte oxidative metabolism is now possible through the use of recombinant interferon-gamma. In vitro studies have shown that neutrophils and monocytes derived from patients with autosomal recessive cytochrome b-positive CGD respond to interferon-gamma with an enhanced respiratory burst (superoxide production) and increased bactericidal activity. Furthermore, subcutaneous interferon-gamma administration improves bactericidal activity in neutrophils and monocytes derived from patients with X-linked, cytochrome b-negative CGD, despite the lack of effect on superoxide production. This suggests that interferon-gamma also stimulates nonoxidative bactericidal pathways. Data from a multicenter clinical trial indicate sustained administration of interferon-gamma is effective in the management of CGD. In addition, related studies indicate that modern molecular and genetic technologies offer the possibility of improved management or cure for CGD.
Gallin
J I
JI
Bacterial Diseases Section, National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, Maryland 20892.
D002648:Child; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use
D007371:Interferon-gamma; D011241:Prednisone