Disparate Effects of Interferon-'y and Tumor Necrosis Factor-a on Early Neutrophil Respiratory Burst and Fungicidal Responses to Candida albicans Hyphae In Vitro

We examined effects of priming with recombinant human inter-feron-y (IFN) or tumor necrosis factor-a (TNF) on neutrophil responses to Candida albicans hyphae. Both cytokines in-creased early superoxide generation after hyphal stimulation. The more pronounced effects of TNF were accompanied by an augmented surface membrane depolarization rate and were in-sensitive to both pertussis toxin and calcium ion chelation, but were negated by concomitant incubation with puromycin or cy-cloheximide during priming. IFN augmented hyphal killing de-spite its only minor enhancement of early respiratory burst re-sponses, but TNF reduced neutrophil fungicidal activity to nearly 40 % below those by unprimed control cells even though it enhanced early superoxide responses more dramatically. Though TNF-primed neutrophils killed hyphae at normal ini-tial rates, IFN-primed or even unprimed cells manifested more fungicidal sustained activity. These disparate consequences of cytokine priming on hyphal destruction were paralleled by dif-ferences in late generation of potentially candidacidal oxidants, hydrogen peroxide, and hypochlorous acid. IFN added during priming failed to correct TNF-associated functional defects in neutrophil anti-Candida responses. Thus, augmentation of early respiratory burst responses to oxidant-sensitive organ-isms need not necessarily reflect concomitant salutary effects on microbicidal activity. (J. Clin. Invest. 1991. 87:711-720.