Effect of omeprazole, lansoprazole, and ranitidine on the DNA synthesis ofmononuclear cells

Objective: To examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells. Design: Ex vivo laboratory study. Setting: Clinical research laboratory of an academic medical center. Subjects: Healthy volunteers. Interventions: None. Measurements and Main Results: Venous blood was collected from normal subje cts and peripheral blood mononuclear cells (PBMCs) were isolated using cent rifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were ad ded to 12-well culture plates in four groups of media: a) central; b) centr al plus lansoprazole (25 mu g/mL); c) control plus omeprazole (0.35 mu g/mL ); and d) control plus ranitidine (50 mu g/mL). PBMCs were exposed to the d rug for 96 hrs, with addition of phytohemagglutinin (2.5 mu g/ mL) for the last 48 hrs, and H-3-thymidine (1 mu Ci) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radioactivity was determine d by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as q uantification of H-3-thymidine uptake. Median disintegrations per min (DPM) /number of PBMCs per well +/- SEM are reported: central 68.3 +/- 37.8; rani tidine 38.4 +/- 94.2; lansoprazole 14.6 +/- 84.4; and omeprazale 15.1 +/- 4 8.9, There was a significant difference between lansoprazole vs. ranitidine (p<.01), and omeprazole vs. ranitidine (p<.05), and no significant differe nce between lansoprazole and omeprazole. Conclusions: This is the first study to compare the potential immunomodulat ing effects of these commonly used agents. Ranitidine caused increased DNA synthesis In PBMCs when compared with lansoprazole and omeprazole. This phe nomenon may be an important, often disregarded, effect of histamine-2-recep tor antagonists when used in postsurgical or trauma patients who have T-lym phocyte-mediated immune suppression.