title: Role of caspofungin in restoring the impaired phagocyte-dependent innate immunity towards Candida albicans in chronic haemodialysis patients.
abstract: Phagocyte-dependent cellular immunity in chronic kidney disease patients undergoing haemodialysis treatment is frequently impaired owing to the uraemic state, resulting in an intrinsic susceptibility to developing invasive fungal infections with high mortality rates. Since synergism between phagocytic cells and antifungal drugs may be crucial for successful therapy, the aim of this study was to evaluate the effects exerted by caspofungin (CAS) on the functional activities of polymorphonuclear cells (PMNs) in haemodialysed patients (HDs) towards Candida albicans compared with those of PMNs from healthy subjects (HSs). PMNs were separated from venous blood samples of 66 HDs and 30 HSs (as controls), and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in the presence of CAS at the minimum inhibitory concentration (MIC) and at sub-MICs. CAS-free controls were also included. In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. In contrast, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. CAS at MIC and sub-MIC levels was able to improve significantly the intracellular fungicidal activity of HD-PMNs against C. albicans, restoring their functionality. These findings provide evidence that CAS exerts a synergistic effect on HD-PMNs against C. albicans, being able to strength the depressed intracellular killing activity. These results corroborate the use of CAS as an effective therapeutic option for the treatment of invasive fungal infections in HDs, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect.
authors: Department of Public Health and Microbiology, University of Turin, Via Santena 9, Turin, Italy.
authors: Daniela
authors: D
authors: Scalas
authors: Giuliana
authors: G
authors: Banche
authors: Chiara
authors: C
authors: Merlino
authors: Franca
authors: F
authors: Giacchino
authors: Valeria
authors: V
authors: Allizond
authors: Giuseppe
authors: G
authors: Garneri
authors: Rosaria
authors: R
authors: Patti
authors: Janira
authors: J
authors: Roana
authors: Narcisa
authors: N
authors: Mandras
authors: Vivian
authors: V
authors: Tullio
authors: Anna Maria
authors: AM
authors: Cuffini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects* / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology; D000077336:Caspofungin; D004357:Drug Synergism; D054714:Echinocandins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000628:therapy; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D006435:Renal Dialysis
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin