Abstract
We evaluated the immunomodulatory effects of three different classes of antifungal agents on the human monocytic cell line, THP-1, which had been stimulated in vitro with Aspergillus fumigatus conidia. Cells treated with amphotericin B (AmB), micafungin (MF), and voriconazole (VCZ), at concentrations not affecting cell viability, reduced production of tumor necrosis factor (TNF)-α in response to conidia, with the greatest reduction noted with VCZ. The reduction of TNF-α production correlated with TNF-α gene expression assessed by PCR and nuclear factor κB (NFκB) levels. Co-stimulation with granulocyte-macrophage colony stimulating factor abolished immunomodulatory effects of the drugs. Antifungal agents affect the immune reaction caused by A. fumigatus conidia in stimulated monocytes at clinically relevant drug concentrations. Because drugs with different mechanisms of action produced this effect, this suggests that it is the result of factors mediated by the cells. The impact of these immunomodulatory effects needs assessment.
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Acknowledgment
Funded in part by the Foundation for Research in Infectious Diseases.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on Early Online on 12 February 2010.