ACTIVITY INHIBITION OF CYTOLYTIC LYMPHOCYTES BY OMEPRAZOLE

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 c ells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and S C 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 c ultured with rhIL-2 and in allo-specific cytotoxic lymphocyte-mediated lysis generated in vitro. A significant inhibition of cytotoxic activ ity 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 inh ibition of lytic activity was obtained after 4 h incubation of effecto r 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 inhib itory effect on NK/LAK activity, suggesting that prostaglandins are no t involved in the process leading to suppression of cytocidal activity . When effector cells were incubated with OM in presence of rhIL-2 (50 0 U/ml), the cytokine failed to antagonize the inhibitory effect of th e drug. On the contrary, if OM pretreated cells were incubated with rh IL-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 rapi d, strong effect on various types of cytotoxic lymphocytes ranging fro m cytotoxicity inhibition to irreversible cell damage.