We have previously reported that BCG induced a rapid and intense augmentation of murine peritoneal natural killer (NK) cell activity. A requirement for macrophages and for soluble NK-enhancing factors was also demonstrated. In the present report we show that BCG-induced peritoneal macrophages secreted large amounts of prostaglandin Ez (PGE2). In vitro, PGEz inhibited both normal splenic NK cells and BCG-induced peritoneal NK cells at concentrations between lo-' and lo-' M, in contrast to the

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... ctive PGFz, isomer. BCG-induced PGEz synthesis was inhibited in vivo with the prostaglandin cyclo-oxygenase inhibitors indomethacin and aspirin. These drugs concommitantly potentiated the BCG-induced augmentation of peritoneal NK cells, although they had only marginal effects on normal NK activity in viuo or in vitro. Pretreatment of BCG-induced peritoneal exudate cells (BCG-PEC) in vitro with indomethacin or aspirin also potentiated the augmentation of normal splenic NK cells by BCG-PEC supernatants in vitro. With these inhibitors of prostaglandin synthesis, there was an inverse correlation, both in vitro and in uiuo, between the levels of PGEz secreted by BCG-induced macrophages and the augmentation of NK activity. Thus, the macrophage appears to play a centra1 role in the regulation of NK activity in BCG-infected mice by way of secreting NKenhancing factors and NK-inhibiting factors, including PGEz. Pharmacologic intervention to manipulate NK activity via control of the secretion of macrophage factors may prove useful in further enhancing the immunotherapeutib effects of BCG. Much of the recent interest concerning the role of natural killer (NK)3 cells in the spontaneous lysis of tumor cells in vivo