Immunomodulatory Effects of Voriconazole and Caspofungin on Human Peripheral Blood Mononuclear Cells Stimulated by Candida albicans and Candida krusei

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-gamma 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-beta 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.