Activity inhibition of cytolytic lymphocytes by omeprazole.

Abstract

This study examined the in vitro effect of omeprazole (OM) on various types of murine cytocidal lymphocytes. The results show that OM caused a strong inhibition of basal natural killer (NK) activity in spleen cells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and SC activated in vivo by injection of maleic anhydride divinyl ether 1,2-copolymer (MVE-2) or inactivated Candida albicans (CA); in lymphokine-activated killer (LAK) activity generated in vitro from splenocytes cultured with rhIL-2 and in allo-specific cytotoxic lymphocyte-mediated lysis generated in vitro. A significant inhibition of cytotoxic activity of all types of effector cells after 30 min incubation was already induced by OM at 1 x 10(-3) M concentration, after 1 h incubation at 5 x 10(-4) M and after 4 h incubation at 1 x 10(-4) M OM. Complete inhibition of lytic activity was obtained after 4 h incubation of effector cells with 1 x 10(-3) M OM. No inhibitory effect was observed at 5 x 10(-5) M OM concentration. Indomethacin did not abrogate the OM inhibitory effect on NK/LAK activity, suggesting that prostaglandins are not involved in the process leading to suppression of cytocidal activity. When effector cells were incubated with OM in presence of rhIL-2 (500 U/ml), the cytokine failed to antagonize the inhibitory effect of the drug. On the contrary, if OM pretreated cells were incubated with rhIL-2 for a further 18 h after drug removal, this cytokine was able to restore NK activity, but only when NK inhibition was incomplete. These results demonstrate for the first time that in vitro OM causes a rapid, strong effect on various types of cytotoxic lymphocytes ranging from cytotoxicity inhibition to irreversible cell damage.