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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

✍ Scribed by Michael J. Brunda; Deborah Rosenbaum; Lorraine Stern


Publisher
John Wiley and Sons
Year
1984
Tongue
French
Weight
600 KB
Volume
34
Category
Article
ISSN
0020-7136

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✦ Synopsis


The effect of a human recombinant hybrid alpha interferon (referred to as rHulFN-alphaA/D) on pulmonary metastases induced by intravenous injection of B16 FIO melanoma cells in C57BU6 mice was examined; rHulFN-alphaAID 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 rHulFN-alphaAID 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 FlO injection resulted in nosignificant 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 vitrocytotoxicity against YAC-I or in vivo pulmonary clearance of B I6 F 10 cells. Pretreatment of mice with 10 daily injections of rHulFN-alphaA/D resulted in decreased N K activity and less inhibition of metastases. Therefore, in this model system, rHulFN-alphaAlD inhibits metastases when given in the appropriate treatment schedule. Furthermore, the data are consistent with the hypothesis that rHulFN-alphaAID-induced inhibition is a consequence of the immunomodulation of N K cells, which prevent the establishment of pulmonary metastases.