In-vitro effects of cilofungin (LY121019), amphotericin B and amphotericin B-deoxycholate on human polymorphonuclear leucocytes.
The in-vitro influence of cilofungin (LY121019) and amphotericin B on human polymorphonuclear leucocytes (PMNs) was studied by a multifunctional approach. Cilofungin at high concentration (greater than or equal to 20 mg/l) increased adherence to plastic and ingestion of Staphylococcus aureus by PMNs in suspension and Candida albicans by adherent PMNs, and slightly decreased MTT reduction and superoxide generation. Amphotericin B and amphotericin B-deoxycholate decreased adherence to plastic (IC50: 5.1 and 8.2 mg/l respectively) and superoxide generation induced by PMA and opsonized zymosan (IC50 1.1 mg/l for amphotericin B-deoxycholate). Variable results were observed for intra-cellular killing and ingestion. The functional assessment was made with four clinical isolates of yeasts (Can. albicans, Can. tropicalis, Can. Torulopsis) (glabrata, Cryptococcus neoformans). The inoculum was preincubated with the antifungals (PRE) or they were added during (PER) or after ingestion (POST) using PMNs in suspension (PRE and PER), or adhering to plastic (PRE, PER and POST). With the scheme PRE, killing was usually increased with amphotericin B-deoxycholate and cilofungin. With Crypt. neoformans, ingestion was also increased by the antifungals and sodium-deoxycholate, probably by altering the capsule. The results of the scheme POST showed that amphotericin B-deoxycholate, but not cilofungin, increased intracellular killing of Can. albicans, Can. tropicalis and Can. glabrata.
Van der Auwera
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P
Service de Médecine Interne, Institut Jules Bordet, Bruxelles, Belgium.
Meunier
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F
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004338:Drug Combinations / Q000494:pharmacology; D054714:Echinocandins; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D010455:Peptides; D010456:Peptides, Cyclic; D013778:Tetrazolium Salts; D013844:Thiazoles; D003840:Deoxycholic Acid; D013481:Superoxides; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; C042101:cilofungin; C022616:thiazolyl blue; D002118:Calcium