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.