Inhibition of murine natural killer cell activity by prostaglandins.

Abstract

The effect of prostaglandins (PG) on murine natural killer (NK) cell activity was examined. The addition of PGE1, PGE2, PGA1, or PGA2 to the cytotoxicity assay resulted in marked depression of NK activity, whereas addition of PGB1, PGB2, PGF1α, or PGF2α, resulted in little or no inhibition. The inhibition with PG was dependent on the concentration of PG added, occurred at all effector to target cell ratios, and was independent of the target cell used to measure NK activity. PG-mediated inhibition of NK activity was observed by using splenic effector cells from either euthymic or athymic mice and on both spontaneous and interferon-augmented NK activity. Maximal suppression of activity occurred when PG were present throughout the entire assay period, whereas pretreatment of effector cells with PG had minimal inhibitory effect. The susceptibility of NK activity to PG-mediated suppression could be modulated by overnight incubation of spleen cells at 37 °C, such that PG no longer inhibited NK reactivity. To examine the possible in vivo role of PG as regulators of NK activity, inhibitors of PG synthesis were administered to Moloney murine sarcoma-induced tumor-bearing mice with depressed NK activity. After treatment with indomethacin or aspirin, a marked restoration of NK activity to normal or near normal levels was demonstrated in tumor-bearing animals. These results indicate that PG are potent inhibitors of NK activity in vitro and suggest that under certain conditions PG may inhibit NK activity in vivo.