Ranitidine improves lymphocyte function after severe 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.


METHODS
Randomized, prospective, double-blind study.


METHODS
Surgical intensive care unit of a university Level I trauma center.


METHODS
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.


METHODS
Continuous infusion of ranitidine at 6.25 mg/hr (n = 9) or placebo (n = 11) for a maximum of 5 days.


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 assay (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.


CONCLUSIONS
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.
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, USA.
D
D
Rixen
D H
DH
Livingston
P
P
Loder
T N
TN
Denny
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D006259:Craniocerebral Trauma / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology* / Q000517:prevention & control*; D015600:Glasgow Coma Scale; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D015601:Injury Severity Score; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011899:Ranitidine / Q000008:administration & dosage / Q000627:therapeutic use*
D006635:Histamine H2 Antagonists; D007371:Interferon-gamma; D011899:Ranitidine