Indomethacin inhibits kidney metastasis in Bomirski melanoma-bearing hamsters, and modulates natural killer cytotoxic activity of tumor hosts in vivoand in vitro

Natural killer (NK) cells are thought to play an important role in the cont rol of metastatic dissemination. Therefore, stimulation of cytotoxic activi ty of NK cells against neoplastic cells could be preventive for metastatic spread Bomirski amelanotic (Ab) melanoma of Syrian hamster is a transplanta ble tumor metastasizing preferably to the kidneys. During growth of the mel anoma a significant depression of cytotoxic activity of NK cells of tumor h osts is observed. Treatment of melanoma-bearing hamsters with indomethacin provided in drinking water resulted in the increase of NK cytotoxic activit y of blood cells and in the lower occurrence of kidney metastasis. Spleen c ells obtained from healthy and melanoma-bearing hamsters were cultured in v itro with agents influencing NK activity We found an augmentative effect of human interleukin 2 (IL2) and human tumor necrosis factor (TNF). We also o bserved the synergistic effect of IL2/TNF combination, which was present in both groups of animals. The stimulatory effects of cytokines could be pote ntiated by the additional supplementation of cultures with indomethacin. Si milar experiments were performed on spleen cells isolated from the healthy and tumor-bearing animals treated in vivo with indomethacin. Also, in this group of hamsters in vitro stimulation of NK cell activity by the cytokines was effective. The studies presented may give insight into the pathogenesi s of immune abnormalities seen in advanced stages of progression of Ab mela noma, and can provide an experimental basis for immunomodulation in this tu mor model of spontaneous metastasis.