Sydor R. Immunomodulatory effects of opioid and nonsteroidal analgesia for surgical tumor resection

It was found that the use of both selective inhibitor of cyclooxygenase-2 parecoxib and non-selective cyclooxygenases inhibitor dexketoprofen led to the prolonged postoperative survival of experimental animals in comparison with the opioid analgesia. Non-steroidal analgesic drugs also contribute to the maintaining of postoperative immune activity on higher level compared to opioid analgesic drug omnopon. Thus, phagocytic activity of granulocytes and monocytes of the peripheral blood and spleen of experimental animals was at higher levels compared to the use of opioid analgesic omnopon. In addition to that, administration of cyclooxygenase-2 inhibitors for perioperative analgesia in experimental tumor resection resulted in higher postsurgical cytotoxic activity of natural killer cells and significantly increased proliferative response of splenocytes to T cell mitogen as compared to opioid drug treatment and control groups. It was found that opioid analgesia significantly increases molecular markers of immune suppression in sentinel lymph nodes. Administration of omnopon in contrast to non-steroidal analgesics resulted in the postsurgical elevation of mRNA expression levels of TGF-beta and transcriptional factor FoxP3, which are the markers of regulatory T cells. Additionally, with the use of opioid analgesia gene expression of Th2 type cytokines - IL-4 and IL-10, were also amplified in the sentinel lymph nodes of mice after the surgical removal of tumor, what represents a negative effect on the anti-tumor resistance of the organism. New data on the positive immunomodulatory effect of non-steroidal analgesics in the perioperative period were obtained from clinical study. It was proved that the use of nonsteroidal anti-inflammatory drugs for perioperative analgesia in patients with renal cell carcinoma while exerting sufficient analgesic effect contribute to maintaining the activity of the cellular immune response after surgical procedure. This was reflected by increased amounts of IFN-gamma+ T lymphocytes and higher quantity and cytotoxic activity of natural killer cells. The results obtained experimentally justify the feasibility of developing new schemes of analgesia in oncological surgery with the use of cyclooxygenase 2 inhibitors and decrease the use of opioid analgesics as a promising approach to reduce perioperative manifestations of immunosuppression and the risk of metastasis in cancer patients.