Ranitidine improves lymphocyte function after sever head injury: Results of a randomized, double-blind study

Objective: To study the immunomodulatory effect of the histamine receptor antagonist, ranitidine, in patients admitted to the intensive care unit after severe head injury, Design: Randomized, prospective, double-blind study, Setting: Surgical intensive care unit of a university Level I trauma center, Patients: Twenty patients admitted with a Glasgow Coma Scale score of <10 who were enrolled as part of a prospective, multicenter trial to assess the impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding. Interventions: Continuous infusion of ranitidine at 6.25 mg/hr (n = 9) or placebo (n = 11) for a maximum of 5 days. Measurements and Main Results: Before the patients were enrolled in the study and on completion of treatment, lymphocyte cell-surface antigen expression was determined by flow cytometry (n = 14 patients); mitogen-stimulated interferon-gamma and interleukin-2 production were measured by enzyme linked immunosorbent as say (n = 19 patients), Treatment with ranitidine, but not placebo, was associated with a significant increase in CD4(+) lymphocytes (33% to 49%; p<.05) and a significant decrease in CD8+ lymphocytes (41% to 27%; p<.05), Also, the mitogen stimulated interferon-gamma production increased from 121 to 269 pg/mL (p<.05) in patients treated with ranitidine, but not in patients treated with placebo, There were no significant differences in interleukin-2 production or circulating B cell concentrations between both groups, Conclusion: This study demonstrates an immunostimulatory effect of the histamine-2-receptor antagonist, ranitidine, both at the cellular and mediator levels in patients after head injury.