title: Immunomodulatory effects of voriconazole and caspofungin on human peripheral blood mononuclear cells stimulated by Candida albicans and Candida krusei.
abstract: BACKGROUND
  Candida infections are frequently associated with high morbidity and mortality rates in immunosuppressed patients. T cell-mediated and phagocytic immunity are the primary protective immune responses against fungal infections. Antifungal agents such as voriconazole and caspofungin enter phagocytic cells and lead to various intracellular activities. In this study, the authors aimed to investigate the immunomodulatory effects of voriconazole and caspofungin on human peripheral blood mononuclear cells (PBMC) stimulated by Candida albicans and Candida krusei.
  
  
  METHODS
  Human PBMC isolation was performed by Ficoll-hypaque density-gradient centrifugation method. Cell proliferation was assessed by colorimetric method using MTT. The cytokine levels in the human PBMC culture supernatants stimulated by C. albicans and C. krusei were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The addition of voriconazole and caspofungin lead to proliferation of PBMC. In the presence of voriconazole and caspofungin, the levels of IL-2, IFN-γ and IL-6 remarkably increased in PBMC stimulated by C. albicans and C. krusei. However, the combination of antifungal drugs and PBMC stimulated by Candida species did not increase the levels of TGF-β and IL-10.
  
  
  CONCLUSIONS
  The results indicate that voriconazole and caspofungin have immunomodulatory effects on human PBMC stimulated by Candida species. The interaction between antifungal drugs and PBMC stimulates Th1-type cytokine secretion. Cytokine stimulation from immune cells can assist in the elimination of fungal pathogens. Therefore, during the treatment of fungal infection, putative immunomodulatory effects of antifungal agents should be taken into account.
authors.affiliation: Department of Medical Microbiology, Department of Infectious Disease (IF, EY, AK, NS), Gazi University, Ankara, Turkey; Ankara Oncology Hospital (MCO), Cancer Research Institute, Ankara, Turkey; and Department of Infectious Disease (MD), Gazi University, Ankara, Turkey.
authors.forename: Isil
authors.initials: I
authors.lastname: Fidan
authors.forename: Emine
authors.initials: E
authors.lastname: Yesilyurt
authors.forename: Ayse
authors.initials: A
authors.lastname: Kalkanci
authors.forename: Sevgi O
authors.initials: SO
authors.lastname: Aslan
authors.forename: Nur
authors.initials: N
authors.lastname: Sahin
authors.forename: Mustafa Chihat
authors.initials: MC
authors.lastname: Ogan
authors.forename: Murat
authors.initials: M
authors.lastname: Dizbay
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000276:immunology; D000077336:Caspofungin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D055666:Lipopeptides; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D007155:Immunologic Factors; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; D000077336:Caspofungin; D065819:Voriconazole