[Home ] [Archive]   [ فارسی ]  
:: ::
:: Volume 15, Issue 2 (May 2021) ::
Qom Univ Med Sci J 2021, 15(2): 110-119 Back to browse issues page
Assessment of the Effects of Cyclooxygenase Inhibitors on the Immune Status Following Surgery in Adult Male Rats
Mohammad Abyari1 , Samad Alimohammadi * 2, Mehrdad Pooyanmehr1 , Ali Ghashghaii1 , Ali Maleki3
1- Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.
2- Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran. , s.alimohammadi@razi.ac.ir
3- Kermanshah University of Medical Sciences
Abstract:   (916 Views)
Background and Objectives: Surgery via different mechanisms causes immunosuppression in the postoperative
period. The aim of the present study was to investigate the effects of preoperative administration
of cyclooxygenase inhibitors on blood levels of Interleukin-2 (IL-2), Interferon-γ (IFN-γ), Tumor
Necrosis Factor-α (TNF-α), white blood cells (WBCs) and lymphocytes.
Methods: Seventy-five male Wistar rats were divided into five groups (n=15 for each group). Group 1 was
gavaged with normal saline for 3 consecutive days without surgery. Group 2 was gavaged with normal
saline for 3 consecutive days. Groups 3 to 5 were gavaged with indomethacin (4 mg/kg) and celecoxib
(7.5 and 15 mg/kg), respectively, for 3 consecutive days. In Groups 2 to 5, one hour after drugs administration
on the third day, laparotomy was used as a surgery pattern. Blood samples were collected 24
hours after surgery and levels IL-2, IFN-γ, TNF-α, WBCs and lymphocytes were determined. Data were
analyzed using one-way ANOVA test.
Results: Based on the results, a decrease in blood levels of IL-2, IFN-γ and lymphocytes along with an
increase in TNF-α and WBCs were observed 24 hours after surgery compared to control rats (P<0.05).
Indomethacin (4 mg/kg) and celecoxib (15 mg/kg) improved the decreased level of IL-2 (P<0.05). There
was no significant difference in IFN-γ and lymphocytes between surgery group and the groups treated
with indomethacin or celecoxib (P>0.05). Also, only celecoxib (15 mg/kg) could decrease the elevated
levels TNF-α and WBCs (P<0.05).
Conclusion: Perioperative use of cyclooxygenase inhibitors can improve immune system function.
Keywords: Immune system, Cyclooxygenase inhibitors, Surgery, Rat
Full-Text [PDF 4773 kb]   (497 Downloads)    
Type of Study: Original Article | Subject: فیزیولوژی
Received: 2021/05/2 | Accepted: 2021/05/16 | Published: 2021/04/19
1. Choy MC, Visvanathan K, De Cruz P. An overview of the innate and adaptive immune system in inflammatory bowel disease. Inflamm Bowel Dis. 2017; 23(1):2-13. [DOI:10.1097/MIB.0000000000000955] [PMID] [DOI:10.1097/MIB.0000000000000955]
2. Hari MS, Summers C. Major surgery and the immune system: from pathophysiology to treatment. Curr Opin Crit Care. 2018; 24(6):588-93. [DOI:10.1097/MCC.0000000000000561] [PMID] [DOI:10.1097/MCC.0000000000000561]
3. Hogan BV, Peter MB, Shenoy HG, Horgan K, Hughes TA. Surgery induced immunosuppression. Surgeon. 2011; 9(1):38-43. [DOI:10.1016/j.surge.2010.07.011] [PMID] [DOI:10.1016/j.surge.2010.07.011]
4. Roxo AC, Del Pino Roxo C, Marques RG, Rodrigues NCP, Carneiro DV, Souto FMDC, et al. Endocrine-metabolic response in patients undergoing multiple body contouring surgeries after massive weight loss. Aesthet Surg J. 2019; 39(7):756-64. [DOI:10.1093/asj/sjy195] [PMID] [DOI:10.1093/asj/sjy195]
5. Tian XS, Tong YW, Li ZQ, Li LX, Zhang T, Ren TY, et al. Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice. CNS Neurosci Ther. 2015; 21(5):398-409. [DOI:10.1111/cns.12368] [PMID] [PMCID] [DOI:10.1111/cns.12368]
6. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011; 335(1):2-13. [DOI:10.1016/j.mce.2010.04.005] [PMID] [PMCID] [DOI:10.1016/j.mce.2010.04.005]
7. Prenek L, Litvai T, Balázs N, Kugyelka R, Boldizsár F, Najbauer J, et al. Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4+ T cells. Apoptosis. 2020; 25(9-10):715-29. [DOI:10.1007/s10495-020-01629-x] [PMID] [PMCID] [DOI:10.1007/s10495-020-01629-x]
8. Neeman E, Zmora O, Ben-Eliyahu S. A new approach to reducing postsurgical cancer recurrence: perioperative targeting of catecholamines and prostaglandins. Clin Cancer Res. 2012; 18(18):4895-902. [DOI:10.1158/1078-0432.CCR-12-1087] [PMID] [PMCID] [DOI:10.1158/1078-0432.CCR-12-1087]
9. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve-an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000; 52(4):595-638. [PMID]
10. Seth R, Tai LH, Falls T, de Souza CT, Bell JC, Carrier M, et al. Surgical stress promotes the development of cancer metastases by a coagulation-dependent mechanism involving natural killer cells in a murine model. Ann Surg. 2013; 258(1):158-68. [DOI:10.1097/SLA.0b013e31826fcbdb] [PMID] [DOI:10.1097/SLA.0b013e31826fcbdb]
11. Kawashima M, Ogura N, Akutsu M, Ito K, Kondoh T. The anti‐inflammatory effect of cyclooxygenase inhibitors in fibroblast‐like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production. J Oral Pathol Med. 2013; 42(6):499-506. [DOI:10.1111/jop.12045] [PMID] [PMCID] [DOI:10.1111/jop.12045]
12. Li T, Zhang Q, Jiang Y, Yu J, Hu Y, Mou T, et al. Gastric cancer cells inhibit natural killer cell proliferation and induce apoptosis via prostaglandin E2. Oncoimmunology. 2016; 5(2):e1069936. [DOI:10.1080/2162402X.2015.1069936] [PMID] [PMCID] [DOI:10.1080/2162402X.2015.1069936]
13. Wang D, DuBois RN. The role of prostaglandin E2 in tumor-associated immunosuppression. Trends Mol Med. 2016; 22(1):1-3. [DOI:10.1016/j.molmed.2015.11.003] [PMID] [PMCID] [DOI:10.1016/j.molmed.2015.11.003]
14. Yakar I, Melamed R, Shakhar G, Shakhar K, Rosenne E, Abudarham N, et al. Prostaglandin E2 suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Ann Surg Oncol. 2003; 10(4):469-79. [DOI:10.1245/ASO.2003.08.017] [PMID] [DOI:10.1245/ASO.2003.08.017]
15. Khayyal MT, El-Ghazaly MA, El-Hazek RM, Nada AS. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats. Inflammopharmacology. 2009; 17(5):255-66. [DOI:10.1007/s10787-009-0014-z] [PMID] [DOI:10.1007/s10787-009-0014-z]
16. Banti CN, Hadjikakou SK. Non‐steroidal anti‐inflammatory drugs (NSAIDs) in metal complexes and their effect at the cellular level. Eur J Inorg Chem. 2016; 2016(19):3048-71. [DOI:10.1002/ejic.201501480] [DOI:10.1002/ejic.201501480]
17. Liao W, Lin JX, Leonard WJ. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity. 2013; 38:13-25. [DOI:10.1016/j.immuni.2013.01.004] [PMID] [PMCID] [DOI:10.1016/j.immuni.2013.01.004]
18. Zaidi MR, Merlino G. The two faces of interferon-γ in cancer. Clin Cancer Res. 2011; 17(19):6118-24. [DOI:10.1158/1078-0432.CCR-11-0482] [PMID] [PMCID] [DOI:10.1158/1078-0432.CCR-11-0482]
19. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M. Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA. 2010; 107(47):20518-22. [DOI:10.1073/pnas.1014557107] [PMID] [PMCID] [DOI:10.1073/pnas.1014557107]
20. Inada T, Asai T, Yamada M, Shingu K. Propofol and midazolam inhibit gastric emptying and gastrointestinal transit in mice. Anesth Analg. 2004; 99(4):1102-6. [DOI:10.1213/01.ANE.0000130852.53082.D5] [PMID] [DOI:10.1213/01.ANE.0000130852.53082.D5]
21. Benish M, Bartal I, Goldfarb Y, Levi B, Avraham R, Raz A, et al. Perioperative use of β-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol. 2008; 15(7):2042-52. [DOI:10.1245/s10434-008-9890-5] [PMID] [PMCID] [DOI:10.1245/s10434-008-9890-5]
22. Galluzzi L, Yamazaki T, Kroemer G. Linking cellular stress responses to systemic homeostasis. Nat Rev Mol Cell Biol. 2018; 19(11):731-45. [DOI:10.1038/s41580-018-0068-0] [PMID] [DOI:10.1038/s41580-018-0068-0]
23. Iwasaki M, Edmondson M, Sakamoto A, Ma D. Anesthesia, surgical stress, and "long-term" outcomes. Acta Anaesthesiol Taiwan. 2015; 53(3):99-104. [DOI:10.1016/j.aat.2015.07.002] [PMID] [DOI:10.1016/j.aat.2015.07.002]
24. Dąbrowska AM, Słotwiński R. The immune response to surgery and infection. Cent Eur J Immunol. 2014; 39(4):532-7. [DOI:10.5114/ceji.2014.47741] [PMID] [PMCID] [DOI:10.5114/ceji.2014.47741]
25. Hahn T, Alvarez I, Kobie JJ, Ramanathapuram L, Dial S, Fulton A, et al. Short‐term dietary administration of celecoxib enhances the efficacy of tumor lysate‐pulsed dendritic cell vaccines in treating murine breast cancer. Int J Cancer. 2006; 118(9):2220-31. [DOI:10.1002/ijc.21616] [PMID] [DOI:10.1002/ijc.21616]
26. Vuilleumier PH, Schliessbach J, Curatolo M. Current evidence for central analgesic effects of NSAIDs: an overview of the literature. Minerva Anestesiol. 2018; 84(7):865-70. [DOI:10.23736/S0375-9393.18.12607-1] [PMID] [DOI:10.23736/S0375-9393.18.12607-1]
27. Ikegami R, Sugimoto Y, Segi E, Katsuyama M, Karahashi H, Amano F, et al. The expression of prostaglandin E receptors EP2 and EP4 and their different regulation by lipopolysaccharide in C3H/HeN peritoneal macrophages. J Immunol. 2001; 166(7):4689-96. [DOI:10.4049/jimmunol.166.7.4689] [PMID] [DOI:10.4049/jimmunol.166.7.4689]
28. Harizi H, Juzan M, Grosset C, Rashedi M, Gualde N. Dendritic cells issued in vitro from bone marrow produce PGE2 that contributes to the immunomodulation induced by antigen-presenting cells. Cell Immunol. 2001; 209(1):19-28. [DOI:10.1006/cimm.2001.1785] [PMID] [DOI:10.1006/cimm.2001.1785]
29. Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol. 2011; 23(5):598-604. [DOI:10.1016/j.coi.2011.08.003] [PMID] [PMCID] [DOI:10.1016/j.coi.2011.08.003]
30. Faist E, Mewes A, Baker CC, Strasser T, Alkan SS, Rieber P, et al. Prostaglandin E2 (PGE2)-dependent suppression of interleukin alpha (IL-2) production in patients with major trauma. J Trauma. 1987; 27(8):837-48. [DOI:10.1097/00005373-198708000-00001] [PMID] [DOI:10.1097/00005373-198708000-00001]
31. Bao YS, Zhang P, Xie RJ, Wang M, Wang ZY, Zhou Z, et al. The regulation of CD4+ T cell immune responses toward Th2 cell development by prostaglandin E2. Int Immunopharmacol. 2011; 11(10):1599-605. [DOI:10.1016/j.intimp.2011.05.021] [PMID] [DOI:10.1016/j.intimp.2011.05.021]
32. Walker W, Rotondo D. Prostaglandin E2 is a potent regulator of interleukin‐12‐and interleukin‐18‐induced natural killer cell interferon‐γ synthesis. Immunology. 2004; 111(3):298-305. [DOI:10.1111/j.1365-2567.2004.01810.x] [PMID] [PMCID] [DOI:10.1111/j.1365-2567.2004.01810.x]
33. Brogliato AR, Antunes CA, Carvalho RS, Monteiro AP, Tinoco RF, Bozza MT, et al. Ketoprofen impairs immunosuppression induced by severe sepsis and reveals an important role for prostaglandin E2. Shock. 2012; 38(6):620-9. [DOI:10.1097/SHK.0b013e318272ff8a] [PMID] [DOI:10.1097/SHK.0b013e318272ff8a]
34. Toft P, Lillevang ST, Tønnesen E, Svendsen P, Höhndorf K. Redistribution of lymphocytes following E. coli sepsis. Scand J Immunol. 1993; 38(6):541-5. [DOI:10.1111/j.1365-3083.1993.tb03238.x] [PMID] [DOI:10.1111/j.1365-3083.1993.tb03238.x]
35. Chouaib S, Welte K, Mertelsmann R, Dupont B. Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J Immunol. 1985; 135(2):1172-9. [PMID]
36. Grzelak I, Olszewski WL, Engeset A. Suppressor cell activity in peripheral blood in cancer patients after surgery. Clin Exp Immunol. 1983; 51(1):149-56. [PMCID]
37. Hong JY. The effect of preoperative ketorolac on WBC response and pain in laparoscopic surgery for endometriosis. Yonsei Med J. 2005; 46(6):812-7. [DOI:10.3349/ymj.2005.46.6.812] [PMID] [PMCID] [DOI:10.3349/ymj.2005.46.6.812]
38. Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010; 20(2):87-103. [DOI:10.1615/CritRevEukarGeneExpr.v20.i2.10] [PMID] [PMCID] [DOI:10.1615/CritRevEukarGeneExpr.v20.i2.10]
39. Feldmann M, Brennan FM, Elliott M, Katsikis P, Maini RN. TNF alpha as a therapeutic target in rheumatoid arthritis. Circ Shock. 1994; 43(4):179-84. [PMID]
40. Grijalva CG, Chen L, Delzell E, Baddley JW, Beukelman T, Winthrop KL, et al. Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. Jama. 2011; 306(21):2331-9. [DOI:10.1001/jama.2011.1692] [PMID] [PMCID] [DOI:10.1001/jama.2011.1692]
41. Ma Y, Cheng Q, Wang E, Li L, Zhang X. Inhibiting tumor necrosis factor α signaling attenuates postoperative cognitive dysfunction in aged rats. Mol Med Rep. 2015; 12(2):3095-100. [DOI:10.3892/mmr.2015.3744] [PMID] [DOI:10.3892/mmr.2015.3744]
42. Baxevanis CN, Papilas K, Dedoussis GV, Pavlis T, Papamichail M. Abnormal cytokine serum levels correlate with impaired cellular immune responses after surgery. Clin Immunol Immunopathol. 1994; 71(1):82-8. [DOI:10.1006/clin.1994.1055] [PMID] [DOI:10.1006/clin.1994.1055]
43. Shinomiya S, Naraba H, Ueno A, Utsunomiya I, Maruyama T, Ohuchida S, et al. Regulation of TNF-α and interleukin-10 production by prostaglandins I2 and E2: Studies with prostaglandin receptor-deficient mice and prostaglandin E-receptor subtype-selective synthetic agonists. Biochem Pharmacol. 2001; 61(9):1153-60. [DOI:10.1016/S0006-2952(01)00586-X] [DOI:10.1016/S0006-2952(01)00586-X]
44. Renz HA, Gong JH, Schmidt AN, Nain MA, Gemsa DI. Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. J Immunol. 1988; 141(7):2388-93. [PMID]
45. Fuccelli R, Fabiani R, Sepporta MV, Rosignoli P. The hydroxytyrosol-dependent increase of TNF-α in LPS-activated human monocytes is mediated by PGE2 and adenylate cyclase activation. Toxicol In Vitro. 2015; 29(5):933-7. [DOI:10.1016/j.tiv.2015.03.022] [PMID] [DOI:10.1016/j.tiv.2015.03.022]
Send email to the article author

Add your comments about this article
Your username or Email:


XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Abyari M, Alimohammadi S, Pooyanmehr M, Ghashghaii A, Maleki A. Assessment of the Effects of Cyclooxygenase Inhibitors on the Immune Status Following Surgery in Adult Male Rats. Qom Univ Med Sci J 2021; 15 (2) :110-119
URL: http://journal.muq.ac.ir/article-1-3124-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 15, Issue 2 (May 2021) Back to browse issues page
مجله دانشگاه علوم پزشکی قم Qom University of Medical Sciences Journal
Persian site map - English site map - Created in 0.07 seconds with 30 queries by YEKTAWEB 4533