title: 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.
authors.affiliation: Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Policlinico Monteluce, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Scaringi
authors.forename: P
authors.initials: P
authors.lastname: Cornacchione
authors.forename: K
authors.initials: K
authors.lastname: Fettucciari
authors.forename: E
authors.initials: E
authors.lastname: Rosati
authors.forename: R
authors.initials: R
authors.lastname: Rossi
authors.forename: P
authors.initials: P
authors.lastname: Marconi
authors.forename: E
authors.initials: E
authors.lastname: Capodicasa
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009853:Omeprazole / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D007376:Interleukin-2; D011994:Recombinant Proteins; D009853:Omeprazole