Preincubation of Candida albicans strains with amphotericin B reduces tumor necrosis factor alpha and interleukin-6 release by human monocytes.
The release of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) by human monocytes stimulated with whole heat-killed Candida albicans CA3 (a clinical isolate) and CA2 (a germ tube-negative mutant) either treated or not treated with amphotericin B was investigated. The optimal release of the cytokines was observed at 24 h of incubation of the yeasts with the monocytes for both TNF-alpha and IL-6. The levels ranged from 10,500 to 19,000 U/ml for TNF-alpha and from 350 to 460 pg/ml for IL-6. Germ tube-negative mutant CA2 induced the release of TNF-alpha at levels significantly (P < 0.05) lower than those induced by clinical isolate CA3, while no major differences were observed between the two strains with regard to their capacity to induce the release of IL-6. In all instances, preincubation of the yeasts with a sublethal concentration of amphotericin significantly reduced cytokine production. These results suggest that drug-induced alterations of fungal outer structures may affect the interactions between the yeasts and the monocytes, resulting in a reduced level of secretion of cytokines.
Raponi
G
G
La Sapienza University of Rome, Italy.
Ghezzi
M C
MC
Mancini
C
C
Filadoro
F
F
D000666:Amphotericin B / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B; D011112:Polymyxin B