ObjectiveTo examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells.DesignEx vivo laboratory study.SettingClinical research laboratory of an academic medical center.SubjectsHealthy volunteers.InterventionsNone.Measurements and Main ResultsVenous blood was collected from normal subjects and peripheral blood mononuclear cells (PBMCs) were isolated using centrifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture plates in four groups of media: a) control; b) control plus lansoprazole (25 [micro sign]g/mL); c) control plus omeprazole (0.35 [micro sign]g/mL); and d) control plus ranitidine (50 [micro sign]g/mL). PBMCs were exposed to the drug for 96 hrs, with addition of phytohemagglutinin (2.5 [micro sign]g/mL) for the last 48 hrs, and3H-thymidine (1 [micro sign]Ci) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radio-activity was determined by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as quantification of3H-thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well +/- SEM are reported: control 68.3 +/- 37.8; ranitidine 38.4 +/- 94.2; lansoprazole 14.6 +/- 84.4; and omeprazole 15.1 +/- 48.9. There was a significant difference between lansoprazole vs. ranitidine (p < .01), and omeprazole vs. ranitidine (p < .05), and no significant difference between lansoprazole and omeprazole.ConclusionsThis is the first study to compare the potential immunomodulating effects of these commonly used agents. Ranitidine caused increased DNA synthesis in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be an important, often disregarded, effect of histamine-2-receptor antagonists when used in postsurgical or trauma patients who have T-lymphocyte-mediated immune suppression. (Crit Care Med 1999; 27:90-94)