Chronic granulomatous disease, a disorder of host defense, is characterized by an impairment in the killing of microbes that results from a defect in the production of Superoxide anion by phagocytes. We examined the efficacy of interferon gamma, a physiologic activator of phagocytic-cell function, in the treatment of the disease. Two subcutaneous injections of recombinant interferon gamma (0.1 mg per square meter of body-surface area per dose) were administered on consecutive days to four patients with the X-linked form of the disease.

Treatment resulted in 5- to 10-fold increases in superoxide production by granulocytes and monocytes; the improvement was sustained for more than two weeks. Granulocyte bactericidal activity rose proportionally. In the two most responsive patients, both phagocytic functions reached the normal range of activity.

In association with these functional changes, we observed an increase in cellular contents of phagocyte cytochrome b (a critical component of the superoxide-producing oxidase) and immunoreactive cytochrome b heavy chain (the product of the gene that is defective in X-linked chronic granulomatous disease). Levels of cytochrome b detected by spectrophotometry rose from near zero to 10 to 50 percent of normal values.

This study demonstrates partial correction of the cellular defects in chronic granulomatous disease by interferon gamma and provides a basis for clinical trials of the agent. (N Engl J Med 1988; 319:146–51.)