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.
The effect of a human recombinant hybrid alpha interferon (referred to as rHuIFN-alphaA/D) on pulmonary metastases induced by intravenous injection of B16 F10 melanoma cells in C57BL/6 mice was examined; rHuIFN-alphaA/D has been previously shown to have anti-viral, anti-proliferative and immunomodulatory activities in murine cells. Pretreatment of mice with 4 daily intraperitoneal injections of rHuIFN-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 rHuIFN-alphaA, a human recombinant alpha interferon subtype which is inactive on murine cells. Treatment of mice with rHuIFN-alphaA/D following B16 F10 injection resulted in no significant inhibition of pulmonary metastases. Mice given a similar treatment regimen of rHuIFN-alphaA/D had elevated natural killer (NK) cell activity as measured by in vitro cytotoxicity against YAC-I or in vivo pulmonary clearance of B16 F10 cells. Pretreatment of mice with 10 daily injections of rHuIFN-alphaA/D resulted in decreased NK activity and less inhibition of metastases. Therefore, in this model system, rHuIFN-alphaA/D inhibits metastases when given in the appropriate treatment schedule. Furthermore, the data are consistent with the hypothesis that rHuIFN-alphaA/D-induced inhibition is a consequence of the immunomodulation of NK cells, which prevent the establishment of pulmonary metastases.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis
D007370:Interferon Type I