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.

Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis

“…52 Third, in vitro studies have shown that acid-suppressive drugs may impair the function of neutrophils and the activity of natural killer cells. [53][54][55][56][57][58][59] Interestingly, the most striking increase in the risk of pneumonia in association with proton pump inhibitors was observed in the first week of use. The risk of pneumonia in association with use of proton pump inhibitors was attenuated, but still significant, between 30 and 180 days.…”

Theeffect of proton pump inhibitors on the gastric mucosal microenvironment

“…3,9,10,12 PPI-induced agranulocytosis and impaired lymphocyte functions have recently been reported. 11,17 The neutrophils that infiltrate gastric mucosa are affected by PPIs. PPIs can attenuate neutrophil adherence to endothelial cells by inhibiting the expression of adhesion molecules.…”

“…8 The first PPI, omeprazole, has been proven to attenuate neutrophil and lymphocyte functions in vitro. [9][10][11][12] PPIs affect the interaction of neutrophils with endothelial cells and attenuate neutrophil association with chemostatic cytokines of gastric mucosa. 2,4,13 However, the effect of PPIs on gastric mucosa and neutrophils has not been thoroughly clarified.…”

Impact of anesthesia for cancer surgery: Continuing Professional Development

“…In contrast, ranitidine enhances NK cell activity and increases Th1:Th2 ratio. [56][57][58][59] A prospective, randomized study of abdominal surgery patients found that ranitidine diminished the postoperative reduction in spontaneous and stimulated NK cell activity but did not significantly change the Th1:Th2 ratio or mononuclear cell responses. 57 …”

“…En revanche, la ranitidine favorise l'activité des cellules NK et augmente le rapport Th1/Th2. [56][57][58][59] Une étude randomisée prospective portant sur des patients subissant une chirurgie abdominale a trouvé que la ranitidine réduisait la diminution postopératoire de l'activité des cellules NK, spontanée et stimulée, mais qu'elle ne modifiait pas de façon significative le rapport Th1/Th2 ou les réponses des cellules mononucléaires. 57 Agonistes des récepteurs adrénergiques alpha-2…”