DOSE-DEPENDENT ENHANCEMENTS BY INTERFERON-GAMMA ON FUNCTIONAL-RESPONSES OF NEUTROPHILS FROM CHRONIC GRANULOMATOUS-DISEASE PATIENTS

Interferon-gamma (IFN-gamma) is recommended as prophylaxis against inf ections in patients with chronic granulomatous disease (CGD). However, since the optimal dose, the dosing interval, and the mechanisms of ac tion are not well-defined, we studied the effects an CGD neutrophil (P MN) functions ex vivo of interferon-gamma (IFN-gamma). Evaluations wer e made on oxidative capacity, measured by superoxide anion production and chemiluminescence after stimulation with f-met-leu-phe (f-MLP) or phorbol-myristate-acetate, the killing of Aspergillus fumigatus hyphae (assessed as conversion of the tetrazolium salt MTT to formazan), and on the expression of Fc gamma RI receptor (CD64). After randomization , 9 CGD patients (4 with gp91(phox), 3 with p47(phox), 1 with p67(phox ) deficiency and 1 with unspecified CGD) were given IFN-gamma, either 50 or 100 mu g/m(2) subcutaneously on 2 consecutive days after double blinded randomization. Furthermore, one female hyperlyonized X-linked carrier with a CGD phenotype was also studied separately after IFN-gam ma treatment. Evaluations were made the day before and on days 1, 3, 8 , and 18 after IFN-gamma administration. The killing of A fumigatus hy phae, being close to zero before lFN-gamma, was enhanced on day 3, bei ng 36% higher than pretreatment values in the high-dose CGD group and 17% in the low-dose group. The expression of Fc gamma RI on PMN increa sed 3.7-fold in the high-dose and 2.3 fold in the low-dose CGD group, being maximal on day 1. Oxidative functions were raised in only select ed patients represented by different subtypes of CGD. The hyperlyonize d carrier of X-linked CGD responded to IFN-gamma with more enhanced ox idative responses and Aspergillus killing of her PMNs than the other p atients. This study suggests that a higher dose of IFN-gamma than curr ently recommended confers transient enhancements of certain PMN functi ons in CGD patients. (C) 1997 by The American Society of Hematology.