Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes.
Many antimycotic agents negatively affect the natural immune response. Typically, these drugs impair polymorphonuclear leukocyte (PMN) production of superoxide anion, chemotaxis, or the killing of pathogens. Allylamines are a new class of antimycotic compounds with a new mechanism of antifungal action, i.e., inhibition of the fungal squalene epoxidase. The trial that we describe aimed to evaluate the effects of two allylamines, terbinafine and naftifine, on selected functions of PMNs, i.e., superoxide anion production, chemotaxis, and killing of Candida albicans blastospores. Terbinafine and naftifine on their own did not affect superoxide anion production when they were added to PMNs. When PMNs were preincubated with allylamines and were then stimulated by N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate, superoxide anion production was increased (priming effect). Since intracellular free calcium (Ca2+i) is involved in the control of superoxide anion production, we evaluated the effects of the allylamines on the Ca2+i concentration ([Ca2+]i). In the presence of terbinafine or naftifine, the [Ca2+]i increased in a dose-dependent manner; the source of Ca2+i was not extracellular since it was not affected by extracellular calcium chelation with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In the presence of terbinafine or naftifine, chemotaxis of PMNs was not impaired. Terbinafine and naftifine slightly but significantly increased the killing of C. albicans blastospores (P < 0.05 at 10 and 100 microM). In conclusion, in contrast to imidazole-like drugs, the allylamine antimycotic compounds terbinafine and naftifine enhance selected functions of PMNs.
Vago
T
T
Servizio di Endocrinologia, Ospedale L. Sacco (Vialba), Milan, Italy.
Baldi
G
G
Colombo
D
D
Barbareschi
M
M
Norbiato
G
G
Dallegri
F
F
Bevilacqua
M
M
D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002176:Candida albicans / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D000077291:Terbinafine
D000935:Antifungal Agents; D009281:Naphthalenes; D013481:Superoxides; D000499:Allylamine; C029178:naftifine; D000077291:Terbinafine; D002118:Calcium