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 Original Articles |
| Effects of Antifungal Agents on the Production of Cytokines from Macrophages Stimulated by Aspergillus fumigatus conidia |
| Eun-Young Kwon, M.D.2, Chulmin Park, M.D.2, Sun Hee Park, M.D.1, Su-Mi Choi, M.D.1, Dong-Gun Lee, M.D.1Jin-Hong Yoo, M.D.1, Wan-Shik Shin, M.D.1 and Jung-Hyun Choi, M.D.1 |
| Division of Infectious Diseases, 1Department of Internal Medicine, College of Medicine, The Catholic University of KoreaCatholic Research Institutes of Medical Science2, The Catholic University of Korea |
Vol.39 Num.1 (p38~45)
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Background:We wanted to evaluate the immunomodulatory effect of three antifungal agents, amphotericin B (AmB), micafungin (MF), itraconazole (ITZ), in the aspect of cytokine production and expression of nuclear factor-κB (NF-κB) in the Aspergillus fumigatus conidia treated-RAW264.7 cells, a murine alveolar macrophage cell line.
Materials and Methods:We evaluated cytotoxic effect of antifungal agents using commercial cell proliferation assay. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 production according to stimulation (control, A. fumigatus conidia only, conidia + antifungal drug, conidia + antifungal drug + GM-CSF) was evaluated and compared each using commercial ELISA method. NF-κB activation was evaluated by western blot analysis.
Results:AmB, MF, ITZ showed dose-dependent cytotoxic effect on the tested cells. Stimulation of cells by A. fumigatus conidia induced TNF-α production. Pretreatment of AmB at concentration not affecting cellular survival did not change the production of TNF-α compared to conidia treated cells, but pretreament of MF or ITZ showed reduced amount of TNF-α production compared to conidia treated cells. AmB also showed synergistic effect on TNF-α production when simultaneously treated with GM-CSF. IL-10 production was markedly increased when the cells were treated with AmB with conidia. MF and ITZ induced less increase of IL-10 production than AmB. AmB also showed synergistic effect on the production of IL-10 when treated with GM-CSF simultaneously. A. fumigatus conidia enhanced expression of NF-κB. The degree of NF-κB expression was associated with the amount of TNF-α and IL-10 produced.
Conclusion:The antifungal agents we used in this experiment showed that decreased TNF-α production and increased IL-10 production from the RAW264.7 cells stimulated by A. fumigatus conidia after pretreatment of antifungal agents. But more studies, such as the association between immunomodulatory effect, antifungal activity and difference of signal pathway of cellular activation according to drugs should be performed. |
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Keywords : Antifungal drug, Immunomodulation, Macrophage |
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