Effects of antifungal agents on the function of human neutrophils in vitro

E. Roilides, T. J. Walsh, M. Rubin, D. Venzon, P. A. Pizzo

Research output: Contribution to journalArticlepeer-review

Abstract

Polymorphonuclear leukocytes (PMNs) are an important component of the host defense against fungi. We investigated the influence of five antifungal agents on PMN function and compared them with amphotericin B (AmB). The in vitro effects of AmB, flucytosine, ketoconazole, fluconazole, Sch-39304, and cilofungin (LY121019) on chemotaxis, phagocytosis, oxidative metabolism of PMN as reflected by superoxide anion (O2-) generation, and intracellular killing of Candida albicans blastoconidia were examined. With regard to chemotaxis in response to N-formylmethionyl-leucyl-phenylalanine, as measured by the multiwell chamber method, AmB induced a marked decrease (≥ 5 μg/ml), whereas ketoconazole at 5 μg/ml enhanced it. Phagocytosis was significantly decreased after pretreatment of PMNs with AmB and Sch-39304 (> 5 and 1 to 10 μg/ml, respectively). O2- production after stimulation of PMNs with N-formylmethionyl-leucyl-phenyl-alanine was significantly decreased by AmB (> 5 μg/ml) and enhanced by Sch-39304 (1 to 5 μg/ml). In contrast, intracellular killing, as tested by methylene blue staining, was enhanced by ketoconazole (5 μg/ml) and Sch-39304 (1 to 5 μg/ml). Flucytosine, fluconazole, and cilofungin did not affect PMN function at therapeutic concentrations. The results of this comprehensive study indicate that AmB, flucytosine, cilofungin, and the newer azoles, at safely achievable concentrations, generally do not suppress PMN function in vitro and may enhance selective functions.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalAntimicrobial agents and chemotherapy
Volume34
Issue number2
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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