EFFECTS OF CYCLOSPORINE-A ON EXPERIMENTAL HEPATIC METASTASES OF MOUSECOLON-26 TUMOR

Cyclosporine A (CSA), an immunosuppressive agent with apparently selec tive effects on T lymphocytes and little myelotoxicity, was tested for its effects on hepatic metastases by inoculation of mouse colon-26 tu mour cells into the portal vein in male CDF1 mice, CSA, given subcutan eously in daily doses of 10 - 50 mg/kg/day, for 22 days, significantly increased the incidence of hepatic nodules. This increase was positiv ely correlated with the CSA dose. When 5-fluorouracil was injected at a dose of 15 mg/kg/day every other day after the inoculation of tumour cells a highly significant reduction in the incidence of metastases w as seen (compared with the controls). This strong inhibitory effect of 5-fluorouracil on metastasis was almost completely suppressed when mi ce were treated with CSA concomitantly. The results suggest that CSA a ffects the host immune system, accelerating the production of hepatic metastases.