RANITIDINE IMPROVES LYMPHOCYTE FUNCTION AFTER SEVER HEAD-INJURY - RESULTS OF A RANDOMIZED, DOUBLE-BLIND-STUDY

Objective: To study the immunomodulatory effect of the histamine recep tor antagonist, ranitidine, in patients admitted to the intensive care unit after severe head injury, Design: Randomized, prospective, doubl e-blind study, Setting: Surgical intensive care unit of a university L evel I trauma center, Patients: Twenty patients admitted with a Glasgo w Coma Scale score of <10 who were enrolled as part of a prospective, multicenter trial to assess the impact of multiple risk factors and ra nitidine prophylaxis on the development of stress-related upper gastro intestinal bleeding. Interventions: Continuous infusion of ranitidine at 6.25 mg/hr (n = 9) or placebo (n = 11) for a maximum of 5 days. Mea surements and Main Results: Before the patients were enrolled in the s tudy and on completion of treatment, lymphocyte cell-surface antigen e xpression 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 wi th ranitidine, but not placebo, was associated with a significant incr ease in CD4(+) lymphocytes (33% to 49%; p<.05) and a significant decre ase in CD8+ lymphocytes (41% to 27%; p<.05), Also, the mitogen stimula ted interferon-gamma production increased from 121 to 269 pg/mL (p<.05 ) in patients treated with ranitidine, but not in patients treated wit h placebo, There were no significant differences in interleukin-2 prod uction or circulating B cell concentrations between both groups, Concl usion: This study demonstrates an immunostimulatory effect of the hist amine-2-receptor antagonist, ranitidine, both at the cellular and medi ator levels in patients after head injury.