Hara E, Ishijima S A, Ochi H, Osumi M, Abe S, Yamaguchi H
Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112, Japan.
Nihon Ishinkin Gakkai Zasshi. 1998;39(1):17-25. doi: 10.3314/jjmm.39.17.
Effects of itraconazole (ITCZ) on anti-Candida activity of a macrophage (MP)-neutrophil axis were examined in vitro. Murine peritoneal MP, stimulated by an enterococcal preparation FK-23, released tumor necrosis factor a (TNF) into the culture medium in 20 hr-culture period. This level of TNF production by the stimulated MP, which were measured by a bioassay or immunological assay, was heightened by co-stimulation with 0.5 mg/ml of ITCZ. Supernatants obtained from the culture medium of FK-23 and ITCZ-treated MP not only contained about 10 ng/ml of TNF but also had the capacity to enhance anti-Candida activity of murine neutrophils. This enhancement was blocked by pretreatment of the MP-supernatant with anti-TNF antibody. Observation by scanning electron microscope suggested that cell walls of the candida mycelia, the growth of which was inhibited by the neutrophils in the presence of either the MP-supernatant or TNF, sustained similar structural damage. These results suggest that ITCZ augments anti-Candida activity of neutrophils through enhanced production of TNF by MP in vitro.
在体外研究了伊曲康唑(ITCZ)对巨噬细胞(MP)-中性粒细胞轴抗念珠菌活性的影响。由肠球菌制剂FK-23刺激的小鼠腹腔MP在20小时培养期内将肿瘤坏死因子α(TNF)释放到培养基中。通过生物测定或免疫测定法测量,经刺激的MP产生的TNF水平在与0.5mg/ml的ITCZ共同刺激下升高。从FK-23和ITCZ处理的MP培养基中获得的上清液不仅含有约10ng/ml的TNF,而且具有增强小鼠中性粒细胞抗念珠菌活性的能力。用抗TNF抗体预处理MP上清液可阻断这种增强作用。扫描电子显微镜观察表明,念珠菌菌丝体的细胞壁在MP上清液或TNF存在下被中性粒细胞抑制生长,其结构持续受到类似损伤。这些结果表明,ITCZ在体外通过增强MP产生TNF来增强中性粒细胞的抗念珠菌活性。