ルイス肺癌マウスモデルでのクラリスロマイシンのサイトカイン発現に及ぼす効果

Abstract

A long-term treatment of clarithromycin (CAM), a 14-membered ring macrolide antibiotic, was shown to increase the median survival time for patients with unresectable non small-cell lung cancer. This study was addressed to determine the effects of CAM treatment on the expression of cytokine mRNA in spleen cells of mice bearing Lewis lung carcinoma (LLC). In mice which were not inoculated with LLC cells, there was no difference in the expression profile of cytokine mRNAs between the CAM-treated group and the non-CAM group. In mice bearing LLC, however, the expressions of mRNAs for IL -4, IL-12 p 40, and IFN-γ was increased, but that of IL-6 mRNA was decreased in the CAM -treated group, compared to the non-CAM group. Administration of anticancer agents, including CDDP and VDS, resulted in the suppresssion of cytokine mRNA expression. The combination therapy of CAM and these anticancer agents restored the expression level of mRNAs for IL-2, IL-4, IL-12, and IFN-γ up to the same level as observed in tumor-bearing mice treated with CAM alone, and also decreased IL-6 mRNA expression. When CAM administration was initiated 1 week after anticancer therapy, these changes for the expres- sion of cytokine mRNAs were more marked. These results suggest that CAM stimulates the well-balanced expansipn of helper T-cell subsets in tumor-bearing hosts recovering from immunosuppression caused by anticancer chemotherapy. Thus, CAM may be a promising adjuvant drug to anti-cancer chemotherapy, and treatment with this macrolide should be initiated after some interval but not immediately after basic cancer therapy.