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Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (1): 31-36    DOI: 10.31083/j.ceog.2020.01.4963
Original Research Previous articles | Next articles
Influence of cytokines on the postoperative period
D. Jovanovic1, *(), D. R. Milovanovic2, I. Jovanovic3, M. Folic2, V. Jakovljevic4, 5
1Department of Anesthesiology and Reanimatology, Clinical Centre "Kragujevac", Kragujevac, Serbia
2Department of Clinical Pharmacology, Clinical Centre "Kragujevac", Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia
3Department of Immunology, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia
4Department of Physiology, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia
5University IM Sechenov, Department of Human Pathology, 1st MOSCOW State Medical, Moscow Russian Federation, Serbia
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Purpose of Investigation: The relationships between postoperative recovery and changes of circulating levels of pro- and anti-inflammatory cytokines. Materials and Methods: The study included prospectively a cohort of 51 females who underwent abdominal hysterectomy for benign diseases. Recovery was assessed with Quality of Recovery 40 (QoR-40) questionnaire and concentrations of four cytokines during the 72-hours period were measured using human sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results: Total QoR-40 score significantly declined on the first and the second postoperative days and then returned to baseline (p < 0.001). Interleukin-17 serum levels had no significant trend (p = 0.072). Statistically significant patterns of concentration changes of interferon gamma (p = 0.010), interleukin-10 (p < 0.001), and transforming growth factor (p = 0.016) were found. There were no significant correlations between QoR-40 scores and concentrations of any cytokine, at prespecified study power for moderate relationships at least. Conclusion: Recovery after abdominal hysterectomy was rapid and complete and it was unrelated to serum concentration profiles of examined cytokines.

Key words:  Hysterectomy      Postoperative recovery      Functional rehabilitation      Cytokines      Interleukins     
Published:  15 February 2020     
*Corresponding Author(s):  D. Jovanovic     E-mail:

Cite this article: 

D. Jovanovic, D. R. Milovanovic, I. Jovanovic, M. Folic, V. Jakovljevic. Influence of cytokines on the postoperative period. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(1): 31-36.

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Figure 1.  — Serum concentrations of IL-17 (pg/mL) in 14 patients receiving morphine plus ketoprofen analgesia at different time points; squares represent medians and vertical bars represent the 25th and 75th percentiles, respectively *p < 0.05.

Table 1  — QoR-40 total score and serum concentration of cytokines in the entire study population in different time points.
Variable Baseline Visit 1 Visit 2 Visit 3 Visit 4
QoR-40 total score 188.6 ± 9.6 n.a. 170.6 ± 11.1* 180.4 ± 11.2* 187.7 ± 6.0
(165-200) (146-189) (152-195) (174-200)
IL-17 (pg/mL) 25.0 ± 21.4 20.4 ± 12.1* 20.3 ± 14.1* 22.8 ± 21.9 22.4 ± 18.7
(7.0-159.0, 23.1) (4.4-71.0, 17.9) (7.1-66.8, 15.5) (3.7-151.0, 16.5) (3.8-129.3, 17.9)
IFN-γ(pg/mL) 740.6 ± 1846.9
(0-11394.8, 60.7)
646.3 ± 1826.6*
(0-10302.7, 71.8)
591.7 ± 1956.5
(0-12845.6, 49.6)
739.8 ± 1845.8
(0-11634.3, 127.6)
255.0 ± 671.8*
(0-3759.2, 38.4)
IL-10 (pg/mL) 77.2 ± 126.4 88.5 ± 108.7 47.0 ± 91.8* 58.7 ± 81.4 45.5 ± 57.5
(0-557.7, 27.7) (10.2-690.8, 56.9) (0-540.1, 19.4) (0-330.5, 28.1) (0-296.6, 12.1)
TGF-β (pg/mL) 34.4 ± 13.6
(14.3-67.8, 32.8)
32.7 ± 14.5
(14.5-80.6, 30.1)
30.5 ± 11.1
(14.2-63.7, 28.8)
29.7 ± 11.6*
(14.8-74.6, 27.8)
27.3 ± 12.8*
(14.0-70.0, 25.7)
Figure 2.  — Changes (absolute differences) of IL-17 concentrations from V0 to V1 (panel A) and from V0 to V2 study period (panelB) in different patient subgroups receiving morphine plus ketorolac (ketorolac), morphine (morphine), morphine plus ketoprofen (ketoprofen) and morphine plus paracetamol (paracetamol), excluding five subjects with numeric pain rating scale score of four at the final visit; the boxplots represent medians with interquartile ranges and whiskers.

[1] Allvin R., Svensson E., Rawal N., Ehnfors M., Kling A.M., Idvall E.: “The Postoperative Recovery Profile(PRP)a multidimensional questionnaire for evaluation of recovery profiles”. J. Eval. Clin. Pract., 2011, 17, 236.
[2] Myles P.S., Weitkamp B., Jones K., Melick J., Hensen S.: “Validity and reliability of a postoperative quality of recovery score: the QoR40”. Br. J. Anaesth., 2000, 84, 11.
[3] Freide K., Mathew J.P., Podgoreanu M.V.: “Genomic basis of perioperative medicine”. In: Barash P.G., Culen B.F., Stoelting R.K., Cahalan M.K., Stock M.C., Ortega R. (eds). Clinical anesthesia. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013, 130.
[4] Watt D.G., Horgan P.G., McMillan D.C.: “Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review”. Surgery., 2015, 157, 362.
[5] Dantzer R., O’Connor J.C., Freund G.G., Johnson R.W., Kelley K.W.: “From inflammation to sickness and depression: when the immune system subjugates the brain”. Nat. Rev. Neurosci., 2008, 9, 46.
[6] Kehlet H., Dahl J. B.: Anaesthesia, surgery, and challenges in postoperative recovery. Lancet, 2003, 362, 1921.
[7] Abeles A., Kwasnicki R.M., Darzi A.: “Enhanced recovery after surgery: current research insights and future direction”. World J. Gastrointest. Surg., 2017, 9, 37
[8] Buvanendran A., Kroin J.S.: “Multimodal analgesia for controlling acute postoperative pain”. Curr. Opin. Anaesthesiol., 2009, 22, 588.
[9] Qian Y.N., Jin W.J., Wang L., Wang H.J.: “Effect of different concentrations of morphine and tramadol on the differentiation of human helper T cells in vitro”. Br. J. Anaesth., 2005, 95, 277.
[10] Cho J.Y.: “Immunomodulatory effect of nonsteroidal anti-inflammatory drugs(NSAIDs) at the clinically available doses”. Arch. Pharm. Res., 2007, 30, 64
[11] Catro-Alves L.J., De Azevedo V.L., De Freitas Braga T.F., Goncalves A.C., De Oliveira G.S. Jr.: “The effect of neuraxial versus general anesthesia techniques on postoperative quality of recovery and analgesia after abdominal hysterectomy: a prospective, randomized, controlled trial”. Anesth. Analg., 2011, 113, 1480.
[12] Fowler M.A., Spiess B.D.: “Postanesthesia recovery”. In: Barash P.G., Culen B.F., Stoelting R.K., Cahalan M.K., Stock M.C., eds. Clinical Anesthesia. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2009, 1421.
[13] Jovanovic I., Radosavljevic G., Pavlovic S., Zdravkovic N., Martinova K., Knezevic M., et al.: “Th-17 cells as novel participant in immunity to breast cancer”. Serb. J. Exp. Clin. Res., 2010, 11, 7
[14] Kluivers K.B., Hendriks J.C., Mol B.W., Bongers M.Y., Vierhout M.E., Brölmann H.A., de Vet H.C.: “Clinimetric properties of 3 instruments measuring postoperative recovery in a gynecologic surgical population”. Surgery, 2008, 144, 12.
[15] Browner W.S., Newman T.B., Hulley S.B.: “Estimating sample size and power: applications and examples, Appendix 6C”. In: Hulley S.B., Cummings S.R., Browner W.S., Grady D., Newman T.B., eds. Designing clinical research. 3th ed. Philadelphia: Lippincott Williams & Wilkins, 2007, 89.
[16] Gornall B.F., Myles P.S., Smith C.L., Burke J.A., Leslie K., Pereira M.J., et al.: “Measurement of quality of recovery using the QoR-40: a quantitative systematic review”. Br. J. Anaesth., 2013, 111, 161
[17] Sprangers M.A., Thong M.S., Bartels M., Barsevick A., Ordoñana J., Shi Q., et al.; GeneQol Consortium.:“Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update”. Qual. Life Res., 2014, 23, 1997.
[18] Voorhees J.L., Tarr A.J., Wohleb E.S., Godbout J.P., Mo X., Sheridan J.F., et al.: “Prolonged restraint stress increases IL-6, reduces IL-10, and causes persistent depressive-like behavior that is reversed by re-combinant IL-10”. PLoS One, 2013, 8, e58488.
[19] Kim J.W., Kim Y.K., Hwang J.A., Yoon H.K., Ko Y.H., Han C., et al.: “Plasma levels of IL-23 and IL-17 before and after antidepressant treatment in patients with major depressive disorder”. Psychiatry In-vestig., 2013, 10, 294.
[20] Bekker A., Haile M., Kline R., Didehvar S., Babu R., Martiniuk F., Urban M.: “The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery”. J. Neurosurg. Anesthesiol., 2013, 25, 16
[21] Matalka K.Z.: “The effect of estradiol, but not progesterone, on the production of cytokines in stimulated whole blood, is concentrationdependent”. Neuro. Endocrinol. Lett., 2003, 24, 185
[22] Kumru S., Godekmerdan A., Yilmaz B.: “Immune effects of surgical menopause and estrogen replacement therapy in perimenopausal women”. J. Reprod. Immunol., 2004, 63, 31
[23] Chachkhiani I., Gürlich R., Maruna P., Frasko R., Lindner J.: “The postoperative stress response and its reflection in cytokine network and leptin plasma levels”. Physiol. Res., 2005, 54, 279
[24] Roy K.K., Gc N., Singhal S., Bharti J., Kumar S., Mitra D.K., et al.: “Impact of energy devices on the post-operative systemic immune response in women undergoing total laparoscopic hysterectomy for benign disease of the uterus”. J. Turk. Ger. Gynecol. Assoc., 2018, 19, 1
[25] Xing Z.M., Zhang Z.Q., Zhang W.S., Liu Y.F.: “Effects of analgesia methods on serum IL-6 and IL-10 levels after cesarean delivery”. Genet. Mol. Res., 2015, 14, 4778
[26] Shah P.P., Desai P.R., Patel A.R., Singh M.S.: “Skin permeating nanogel for the cutaneous codelivery of two antiinflammatory drugs”. Biomaterials, 2012, 33, 1607
[27] Sayin N., Kocacik Uygun D.F., Sallakci N., Filiz S., Yegin O.: “Inhibitory effects of acetylsalicylic acid and ibuprofen on interleukin17 production”. Turk. J. Immunol., 2013, 1, 42.
[28] Le V., Kurnutala L., SchianodiCola J., Ahmed K., Yarmush J., Daniel Eloy J., et al.: “Premedication with intravenous ibuprofen improves recovery characteristics and stress response in adults undergoing laparoscopic cholecystectomy: a randomized controlled trial”. Pain Med., 2016, 17, 1163.
[29] Wijk L., Nilsson K., Ljungqvist O.: “Metabolic and inflammatory responses and subsequent recovery in robotic versus abdominal hysterectomy: a randomised controlled study”. Clin. Nutr., 2018, 37, 99.
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