title: Recombinant human interferon-gamma reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood.
abstract: Monocytes from 19 of 30 patients with the classic phenotype of chronic granulomatous disease of childhood (CGD) responded to 3 days of treatment in culture with recombinant human interferon-gamma (rHuIFN-gamma) at 100 units/ml by producing superoxide after stimulation with phorbol 12-myristate 13-acetate. Cells from 15 of 16 patients with cytochrome b-positive CGD (15 with autosomal and 1 with X chromosome-linked inheritance) and cells from 4 of 14 patients with cytochrome b-negative CGD (13 with X chromosome-linked and 1 with autosomal recessive inheritance) responded. Subcutaneous rHuIFN-gamma (0.01-0.05 mg/m2) administered as a single dose, daily or every other day, for five or six doses to 3 patients whose phagocytes responded to rHuIFN-gamma in vitro resulted in significant improvement in phagocyte bactericidal activity against Staphylococcus aureus and increases in superoxide production. Studies on 1 patient's cells indicated the increases in superoxide production correlated with increased membrane cytochrome b. The effects of rHuIFN-gamma persisted for more than a week following cessation of therapy. Thus, we have demonstrated a partial correction in vivo of these CGD patients' phagocyte defect with rHuIFN-gamma. Moreover, the data suggest that a significant proportion of patients with CGD will respond to rHuIFN-gamma with augmentation of phagocyte microbicidal function.
authors.affiliation: Bacterial Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
authors.forename: J M
authors.initials: JM
authors.lastname: Sechler
authors.forename: H L
authors.initials: HL
authors.lastname: Malech
authors.forename: C J
authors.initials: CJ
authors.lastname: White
authors.forename: J I
authors.initials: JI
authors.lastname: Gallin
mesh_terms: D001770:Blood Bactericidal Activity; D002478:Cells, Cultured; D002648:Child; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013211:Staphylococcus aureus; D013481:Superoxides / Q000096:biosynthesis
chemical_list: D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma