Indomethacin attenuates the immunosuppressive and tumor-promoting effects of surgery

We have previously shown in rats that both intrathecal and systemic analgesia regimens attenuate surgery-induced increases in tumor susceptibility. The current study used indomethacin to assess the role of prostaglandins and inflammation-associated pain in mediating the deleterious effects of surgery on immunity and tumor susceptibility. Male and female Fischer 344 rats were anesthetized with halothane and were either subjected or not to experimental laparotomy, followed by the administration of indomethacin or vehicle. Tumor susceptibility was assessed by the lung retention assay using the syngeneic MADB106 mammary adenocarcinoma cell line, a natural killer (NK)-sensitive tumor that colonizes only in the lungs. Surgery resulted in a 2- to 3.5-fold increase in lung tumor retention, and indomethacin administration significantly reduced this effect in both sexes without affecting unoperated animals. Indomethacin also attenuated the reductions in rearing behavior evident after surgery, suggesting that it relieved abdominal discomfort. Surgery increased interleukin-6 levels and suppressed NK activity per milliliter blood. Indomethacin restored NK activity in both male and female rats but attenuated surgery-induced interleukin-6 increases only in the male rats. These findings further support our previous work implicating pain in mediating the tumor-enhancing effects of surgery and implicate prostaglandins in mediating this effect. If similar relationships occur in humans, controlling postoperative pain and inflammation must become a priority in the management of cancer patients undergoing surgery.