Ranitidine reduces postoperative interleukin-6 induced C-reactive protein synthesis.

Background: The mechanism of post-traumatic immunosuppression is still not known in detail. However, histamine released during trauma and major surgery may play a significant role in the process. Previously, we showed that the histamine-2 receptor antagonist (H2RA), ranitidine, reduced trauma-induced suppression of certain immunological parameters.
Study Design: The effect of perioperative ranitidine on postoperative change in plasma interleukin-6 (IL-6) and serum C-reactive protein (CRP) levels was assessed in 23 women undergoing elective abdominal hysterectomy. The patients were randomized to receive intravenous ranitidine, 100 mg twice a day from skin incision, for two days, followed by oral ranitidine, 150 mg twice a day, for a further three days, or no ranitidine. Interleukin-6 and CRP were analyzed in plasma and serum, respectively, drawn preoperatively and six, 24, 48, and 120 hours after skin incision.
Results: Routine blood analyses, clinical data (except age), duration of surgery, anesthesia, antibiotic prophylaxis, blood loss, and perioperative blood transfusion were similar in the two groups. Interleukin-6 levels were significantly increased in all patients and without difference between the ranitidine-treated and non-ranitidine-treated patients after six, 24, and 48 hours compared to preoperative levels, respectively. C-reactive protein levels were also significantly increased in all patients after 24, 48, and 120 hours, respectively; however, at 48 hours, CRP was significantly reduced in ranitidine-treated patients compared with non-ranitidine-treated patients (p = 0.02).
Conclusions: These results suggest that histamine-2 receptor activation mechanisms may not be involved in postoperative IL-6 synthesis. However, the reduced CRP level in ranitidine-treated patients suggests that H2RAs modulate IL-6 signal transduction in hepatic cells.