Immunomodulatory effects of antifungal agents on the response of human monocytic cells to Aspergillus fumigatus conidia.
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)-alpha in response to conidia, with the greatest reduction noted with VCZ. The reduction of TNF-alpha production correlated with TNF-alpha gene expression assessed by PCR and nuclear factor kappaB (NF kappaB) 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.
Division of Infectious Disease, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea.
Jung-Hyun
JH
Choi
Eun-Young
EY
Kwon
Chul-Min
CM
Park
Su-Mi
SM
Choi
Dong-Gun
DG
Lee
Jin-Hong
JH
Yoo
Wan-Shik
WS
Shin
David A
DA
Stevens
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054714:Echinocandins / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D055666:Lipopeptides / Q000494:pharmacology; D000077551:Micafungin; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology*; D011743:Pyrimidines / Q000494:pharmacology; D013172:Spores, Fungal / Q000276:immunology*; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D007155:Immunologic Factors; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D065819:Voriconazole; D000077551:Micafungin