TY - JOUR
T1 - Effects of antifungal agents on the function of human neutrophils in vitro
AU - Roilides, E.
AU - Walsh, T. J.
AU - Rubin, M.
AU - Venzon, D.
AU - Pizzo, P. A.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
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U2 - 10.1128/AAC.34.2.196
DO - 10.1128/AAC.34.2.196
M3 - Article
C2 - 2158275
AN - SCOPUS:0025181644
SN - 0066-4804
VL - 34
SP - 196
EP - 201
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 2
ER -