Ukr.Biochem.J. 2016; Volume 88, Issue 4, Jul-Aug, pp. 40-47
doi: https://doi.org/10.15407/ubj88.04.040
The effect of perioperative analgesic drugs omnopon and dexketoprofen on the functional activity of immune cells in murine model of tumor surgery
R. I. Sydor1,2, N. M. Khranovska1, O. V. Skachkova1, L. M. Skivka2
1National Cancer Institute, Ministry of Public Health of Ukraine, Kyiv, Ukraine;
2Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: creatogen@gmail.com
We aimed to investigate the effect of perioperative analgesia with nonselective cyclooxygenase-2 inhibitor dexketoprofen and opioid drug omnopon on the functional activity of immune cells in tumor excision murine model. Lewis lung carcinoma cells were transplanted into hind paw of C57/black mice. On the 23th day tumor was removed. Analgesic drugs were injected 30 min before and once a day for 3 days after the surgery. Biological material was obtained a day before, 1 day and 3 days after the tumor removal. IFN-γ, IL-4, IL-10 and TGF-β mRNA levels in splenic cells were assessed by quantitative real-time RT-PCR. Cytotoxic activity of splenocytes was estimated by flow cytometry. We found that in splenocytes of mice received opioid analgesia IL-10 mRNA level was increased 2.3 times on day one after the surgery compared to preoperative level (P < 0.05), while in dexketoprofen group this parameter did not change. IFN-γ gene expression level on day 3 after tumor removal was 40% higher in splenocytes of dexketoprofen treated mice as compared with omnopon treated animals (P < 0.05). Cytotoxic activity of splenocytes on day 3 postsurgery was (62.2 ± 2.4)% in dexketoprofen against (50.2 ± 3.3)% in omnopon group. In conclusion, perioperative analgesia with cyclooxygenase inhibitor dexketoprofen in contrast to opioid analgesia with omnopon preserves higher functional activity of murine immune cells in the experimental model of tumor surgery.
Keywords: cyclooxygenase-2 inhibitor, dexketoprofen, immune cells, omnopon, tumor surgery
References:
- Das J, Kumar S, Khanna S, Mehta Y. Are we causing the recurrence-impact of perioperative period on long-term cancer prognosis: Review of current evidence and practice. J Anaesthesiol Clin Pharmacol. 2014 Apr;30(2):153-9. PubMed, PubMedCentral, CrossRef
- Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Miyazaki M. Immunosuppression following surgical and traumatic injury. Surg Today. 2010 Sep;40(9):793-808. PubMed, CrossRef
- Meserve JR, Kaye AD, Prabhakar A, Urman RD. The role of analgesics in cancer propagation. Best Pract Res Clin Anaesthesiol. 2014 Jun;28(2):139-51. PubMed, CrossRef
- Kaye AD, Patel N, Bueno FR, Hymel B, Vadivelu N, Kodumudi G, Urman RD. Effect of opiates, anesthetic techniques, and other perioperative factors on surgical cancer patients. Ochsner J. 2014 Summer;14(2):216-28. PubMed, PubMedCentral
- Yiannakopoulou E. Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents – implications for cancer treatment and chemoprevention. Cell Oncol (Dordr). 2014 Jun;37(3):167-78. PubMed, CrossRef
- Harris RE. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology. 2009 Apr;17(2):55-67. Review. PubMed, CrossRef
- Lisowska B, Szymańska M, Nowacka E, Olszewska M. Anesthesiology and the cytokine network. Postepy Hig Med Dosw (Online). 2013 Aug 5;67:761-9. Review. PubMed, CrossRef
- Menger MD, Vollmar B. Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg. 2004 Nov;389(6):475-84. Review. PubMed, CrossRef
- Van Elssen CH, Vanderlocht J, Oth T, Senden-Gijsbers BL, Germeraad WT, Bos GM. Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation. Blood. 2011 Sep 1;118(9):2473-82. PubMed, CrossRef
- Sasamura T, Nakamura S, Iida Y, Fujii H, Murata J, Saiki I, Nojima H, Kuraishi Y. Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol. 2002 Apr 26;441(3):185-91. PubMed, CrossRef
- Ninković J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids. 2013 Jul;45(1):9-24. Review. PubMed, PubMedCentral, CrossRef
- Jiang J, Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci. 2013 Jul;34(7):413-23. Review. PubMed, PubMedCentral, CrossRef
- Gu AD, Zhang S, Wang Y, Xiong H, Curtis TA, Wan YY. A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor β receptor signaling. Immunity. 2015 Jan 20;42(1):68-79. PubMed, PubMedCentral, CrossRef
- Lantero A, Tramullas M, Díaz A, Hurlé MA. Transforming growth factor-β in normal nociceptive processing and pathological pain models. Mol Neurobiol. 2012 Feb;45(1):76-86. PubMed, CrossRef
- Ronaldson PT, Finch JD, Demarco KM, Quigley CE, Davis TP. Inflammatory pain signals an increase in functional expression of organic anion transporting polypeptide 1a4 at the blood-brain barrier. J Pharmacol Exp Ther. 2011 Mar;336(3):827-39. PubMed, PubMedCentral, CrossRef
- Pacifici R, di Carlo S, Bacosi A, Pichini S, Zuccaro P. Pharmacokinetics and cytokine production in heroin and morphine-treated mice. Int J Immunopharmacol. 2000 Aug;22(8):603-14. PubMed, CrossRef
- Edwards JP, Emens LA. The multikinase inhibitor sorafenib reverses the suppression of IL-12 and enhancement of IL-10 by PGE₂ in murine macrophages. Int Immunopharmacol. 2010 Oct;10(10):1220-8. PubMed, PubMedCentral, CrossRef
- Gutkin DW, Shurin MR. Clinical evaluation of systemic and local immune responses in cancer: time for integration. Cancer Immunol Immunother. 2014 Jan;63(1):45-57. PubMed, PubMedCentral, CrossRef
- Forget P, De Kock M. Could anaesthesia, analgesia and sympathetic modulation affect neoplasic recurrence after surgery? A systematic review centred over the modulation of natural killer cells activity. Ann Fr Anesth Reanim. 2009 Sep;28(9):751-68. PubMed, CrossRef
- Walker W, Rotondo D. Prostaglandin E2 is a potent regulator of interleukin-12- and interleukin-18-induced natural killer cell interferon-gamma synthesis. Immunology. 2004 Mar;111(3):298-305. PubMed, PubMedCentral, CrossRef
- Yakar I, Melamed R, Shakhar G, Shakhar K, Rosenne E, Abudarham N, Page GG, Ben-Eliyahu S. Prostaglandin e(2) suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Ann Surg Oncol. 2003 May;10(4):469-79. PubMed, CrossRef
