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

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.

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.

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).

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.