Division of Infectious Disease, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea.
Med Mycol. 2010 Aug;48(5):704-9. doi: 10.3109/13693780903471784.
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.
我们评估了三种不同类别的抗真菌药物对体外用烟曲霉孢子刺激的人单核细胞系 THP-1 的免疫调节作用。用浓度不影响细胞活力的两性霉素 B (AmB)、米卡芬净 (MF) 和伏立康唑 (VCZ) 处理细胞，可减少对孢子的肿瘤坏死因子 (TNF)-α的产生，其中 VCZ 的减少最为显著。TNF-α产生的减少与通过 PCR 和核因子 kappaB (NF kappaB) 水平评估的 TNF-α基因表达相关。与粒细胞-巨噬细胞集落刺激因子共刺激可消除药物的免疫调节作用。抗真菌药物在临床相关药物浓度下影响刺激的单核细胞中烟曲霉孢子引起的免疫反应。由于作用机制不同的药物产生了这种作用，这表明这是由细胞介导的因素的结果。需要评估这些免疫调节作用的影响。
