Inhibition of experimentally‐induced murine metastases by recombinant alpha interferon: Correlation between the modulatory effect of interferon treatment on natural killer cell activity and inhibition of metastases

Abstract

The effect of a human recombinant hybrid alpha interferon (referred to as rHulFN-alphaA/D) on pulmonary metastases induced by intravenous injection of B16 F10 melanoma cells in C57BL/6 mice was examined; rHulFN-alphaA/D has been previously shown to have anti-viral, anti-proliferative and immunomodulatory activities in murine cells. Pretreatment of mice with 4 daily intra-peritoneal injections of rHulFN-alphaA/D resulted in a marked decrease in the number of pulmonary metastases. This inhibition was dose-dependent but was not seen when mice were similarly treated with rHulFN-alphaA, a human recombinant alpha interferon subtype which is inactive on murine cells. Treatment of mice with rHulFN-alphaA/D following B16 F10 injection resulted in no significant inhibition of pulmonary metastases. Mice given a similar treatment regimen of rHulFN-alphaA/D had elevated natural killer (NK) cell activity as measured by in vitro cytotoxicity against YAC-1 or in vivo pulmonary clearance of B16 F10 cells. Pretreatment of mice with 10 daily injections of rHulFN-alphaA/D resulted in decreased NK activity and less inhibition of metastases. Therefore, in this model system, rHulFN-alphaA/D inhibits metastases when given in the appropriate treatment schedule. Furthermore, the data are consistent with the hypothesis that rHulFN-alphaA/D-induced inhibition is a consequence of the immunomodulation of NK cells, which prevent the establishment of pulmonary metastases.