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The growth endocrine axis and inflammatory responses after laparoscopic cholecystectomy

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Abstract

OBJECTIVE: It is well known that conventional surgery leads to detrimental immune and catabolic responses, thus there is growing interest in the effect of minimally invasive techniques on postoperative endocrine and immune function. The aim of this prospective study was to evaluate the growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/IGF binding protein-3 (IGFBP-3) axis and acute phase (interleukin-6, IL-6, and C-reactive protein, CRP) responses in patients who underwent laparoscopic cholecystectomy. DESIGN: Twenty-nine patients (16 women, 13 men; age: 58±8 years) with a history of uncomplicated symptomatic cholelithiasis participated in the study. Blood samples were collected prior to and at 24 hrs and 48 hrs after laparoscopic cholecystectomy. Serum concentrations of GH, IGF-1, IGFBP-3, and IL-6 were determined by standard sandwich enzyme-linked immunosorbent assay (ELISA), while CRP was measured by nephelometry. ANOVA with repeated measures and Tukey’s post-hoc test were used to evaluate changes in serum measurements. RESULTS: The laparoscopic cholecystectomy resulted in a significant postoperative increase in circulating levels of IL-6 (p=0.031), which is the main cytokine responsible for inducing the acute inflammatory response, and of the acute phase protein CRP (p=0.005). A significant increase in GH levels at 24 hrs (p=0.034) and decrease of IGF-1 on both postoperative days were also found (p=0.045, 0.044), while no changes were documented in IGFBP-3 levels. Significant correlations were revealed between postoperative levels of the acute phase proteins and growth axis hormones (p<0.05 − 0.001). CONCLUSIONS: Our findings suggest that laparoscopic cholecystectomy induces acute phase endocrine and immune responses. These changes may represent a state of systemic inflammation and GH resistance, compatible with possible cytokine-induced anti-anabolic or catabolic effects even after this minimally invasive cholecystectomy.

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References

  1. Buunen M, Gholghesaei M, Veldkamp R, Meijer DW, Bonjer HJ, Bouvy ND, 2004 Stress response to laparoscopic surgery: a review. Surg Endosc 18: 1022–1028.

    Article  PubMed  CAS  Google Scholar 

  2. Veenhof AA, Vlug MS, van der Pas MH, et al, 2012 Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: a randomized trial. Ann Surg 255: 216–221.

    Article  PubMed  CAS  Google Scholar 

  3. Sista F, Schietroma M, Santis GD, et al, 2013 Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis. World J Gastrointest Surgr 5: 73–82.

    Article  Google Scholar 

  4. Madureira FA, Manso JE, Madureira Filho D, Iglesias AC, 2014 Inflammation in laparoendoscopic single-site surgery versus laparoscopic cholecystectomy. Surg Innov 21: 263–268.

    Article  PubMed  Google Scholar 

  5. Jacobi CA, Ordemann J, Zieren HU, et al, 1998 Increased systemic inflammation after laparotomy vs laparoscopy in an animal model of peritonitis. Arch Surg 133: 258–262.

    Article  PubMed  CAS  Google Scholar 

  6. Karamanakos SN, Sdralis E, Panagiotopoulos S, Kehagias I, 2010 Laparoscopy in the emergency setting: a retrospective review of 540 patients with acute abdominal pain. Surg Laparosc Endosc Percutan Tech 20: 119–124.

    Article  PubMed  Google Scholar 

  7. Targarona EM, Pons MJ, Balague C, et al, 1996 Acute phase is the only significantly reduced component of the injury response after laparoscopic cholecystectomy. World J Surg 20: 528–534.

    Article  PubMed  CAS  Google Scholar 

  8. Hendolin HI, Paakonen ME, Alhava EM, Tarvainen R, Kemppinen T, Lahtinen P, 2000 Laparoscopic or open cholecystectomy: a prospective randomised trial to compare postoperative pain, pulmonary function, and stress response. Eur J Surg 166: 394–399.

    Article  PubMed  CAS  Google Scholar 

  9. Chatzimavroudis G, Pavlidis TE, Koutelidakis I, et al, 2009 CO(2) pneumoperitoneum prolongs survival in an animal model of peritonitis compared to laparotomy. J Surg Res 152: 69–75.

    Article  PubMed  Google Scholar 

  10. Boo YJ, Kim WB, Kim J, et al, 2007 Systemic immune response after open versus laparoscopic cholecystectomy in acute cholecystitis: a prospective randomized study. Scand J Clin Lab Invest 67: 207–214.

    Article  PubMed  CAS  Google Scholar 

  11. Sorbello AA, Azevedo JL, Osaka JT, Damy S, Franca LM, Tolosa EC, 2010 Protective effect of carbon dioxide against bacterial peritonitis induced in rats. Surg Endosc 24: 1849–1853.

    Article  PubMed  Google Scholar 

  12. Reith HB, Kaman S, Mittelkotter O, Kilic Y, Kozuschek W, 1997 Cytokine activation in patients undergoing open or laparoscopic cholecystectomy. Int Surg 82: 389–393.

    PubMed  CAS  Google Scholar 

  13. Bellon JM, Manzano L, Larrad A, Honduvilla GN, Bujan J, Alvarez-Mon M, 1998 Endocrine and immune response to injury after open and laparoscopic cholecystectomy. Int Surg 83: 24–27.

    PubMed  CAS  Google Scholar 

  14. Desborough JP, 2000 The stress response to trauma and surgery. Br J Anaesth 85: 109–117.

    Article  PubMed  CAS  Google Scholar 

  15. Helmy SA, Wahby MA, El-Nawaway M, 1999 The effect of anaesthesia and surgery on plasma cytokine production. Anaesthesia 54: 733–738.

    Article  PubMed  CAS  Google Scholar 

  16. Philippou A, Maridaki M, Theos A, Koutsilieris M, 2012 Cytokines in muscle damage. Adv Clin Chem 58: 49–87.

    Article  PubMed  CAS  Google Scholar 

  17. Philippou A, Bogdanis G, Maridaki M, Halapas A, Sourla A, Koutsilieris M, 2009 Systemic cytokine response following exercise-induced muscle damage in humans. Clin Chem Lab Med 47: 777–782.

    Article  PubMed  CAS  Google Scholar 

  18. Kehlet H, 1997 Laparoscopic surgery—where do we stand? Nord Med 112: 280–282.

    PubMed  CAS  Google Scholar 

  19. Ohlsson C, Mohan S, Sjogren K, et al, 2009 The role of liver-derived insulin-like growth factor-I. Endocr Rev 30: 494–535.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Barton ER, Park S, James JK, et al, 2012 Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production. FASEB J 26: 3691–3702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Philippou A, Maridaki M, Pneumaticos S, Koutsilieris M, 2014 The complexity of the IGF1 gene splicing, posttranslational modification and bioactivity. Mol Med 20: 202–214.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Balcells J, Moreno A, Audi L, Roqueta J, Iglesias J, Carrascosa A, 2001 Growth hormone/insulin-like growth factors axis in children undergoing cardiac surgery. Crit Care Med 29: 1234–1238.

    Article  PubMed  CAS  Google Scholar 

  23. Mesotten D, Van den Berghe G, 2006 Changes within the GH/IGF-I/IGFBP axis in critical illness. Crit Care Clin 22: 17–28.

    Article  PubMed  CAS  Google Scholar 

  24. Cerejeira J, Batista P, Nogueira V, Vaz-Serra A, Mukaetova-Ladinska EB, 2013 The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis. J Geriatr Psychiatry Neurol 26: 185–194.

    Article  PubMed  Google Scholar 

  25. Ortega AE, Peters JH, Incarbone R, et al, 1996 A prospective randomized comparison of the metabolic and stress hormonal responses of laparoscopic and open cholecystectomy. J Am Coll Surg 183: 249–256.

    PubMed  CAS  Google Scholar 

  26. Karayiannakis AJ, Makri GG, Mantzioka A, Karousos D, Karatzas G, 1997 Systemic stress response after laparoscopic or open cholecystectomy: a randomized trial. Br J Surg 84: 467–471.

    Article  PubMed  CAS  Google Scholar 

  27. Batrinos ML, Panitsa-Faflia C, Koutsoumanis C, Vourlioti T, Koutsilieris M, 1999 Surgical stress induces a marked and sustained increase of adrenal androgen secretion in postmenopausal women. In Vivo 13: 147–150.

    PubMed  CAS  Google Scholar 

  28. Ohzato H, Yoshizaki K, Nishimoto N, et al, 1992 Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. Surgery 111: 201–209.

    PubMed  CAS  Google Scholar 

  29. Kloosterman T, von Blomberg BM, Borgstein P, Cuesta MA, Scheper RJ, Meijer S, 1994 Unimpaired immune functions after laparoscopic cholecystectomy. Surgery 115: 424–428.

    PubMed  CAS  Google Scholar 

  30. Ueo H, Honda M, Adachi M, et al, 1994 Minimal increase in serum interleukin-6 levels during laparoscopic cholecystectomy. Am J Surg 168: 358–360.

    Article  PubMed  CAS  Google Scholar 

  31. Kristiansson M, Saraste L, Soop M, Sundqvist KG, Thorne A, 1999 Diminished interleukin-6 and C-reactive protein responses to laparoscopic versus open cholecystectomy. Acta Anaesthesiol Scand 43: 146–152.

    Article  PubMed  CAS  Google Scholar 

  32. Gupta A, Watson DI, 2001 Effect of laparoscopy on immune function. Br J Surg 88: 1296–1306.

    Article  PubMed  CAS  Google Scholar 

  33. Schietroma M, Carlei F, Franchi L, et al, 2004 A comparison of serum interleukin-6 concentrations in patients treated by cholecystectomy via laparotomy or laparoscopy. Hepatogastroenterology 51: 1595–1599.

    PubMed  CAS  Google Scholar 

  34. Kirman I, Poltaratskaia N, Cekic V, et al, 2004 Depletion of circulating insulin-like growth factor binding protein 3 after open surgery is associated with high interleukin-6 levels. Dis Colon Rectum 47: 911–918.

    Article  PubMed  Google Scholar 

  35. Harmon GD, Senagore AJ, Kilbride MJ, Warzynski MJ, 1994 Interleukin-6 response to laparoscopic and open colectomy. Dis Colon Rectum 37: 754–759.

    Article  PubMed  CAS  Google Scholar 

  36. Glaser F, Sannwald GA, Buhr HJ, et al, 1995 General stress response to conventional and laparoscopic cholecystectomy. Ann Surg 221: 372–380.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. O’Connor JC, McCusker RH, Strle K, Johnson RW, Dantzer R, Kelley KW, 2008 Regulation of IGF-I function by proinflammatory cytokines: at the interface of immunology and endocrinology. Cell Immunol 252: 91–110.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Liu JL, Yakar S, LeRoith D, 2000 Mice deficient in liver production of insulin-like growth factor I display sexual dimorphism in growth hormone-stimulated postnatal growth. Endocrinology 141: 4436–4441.

    Article  PubMed  CAS  Google Scholar 

  39. Hayes VY, Urban RJ, Jiang J, Marcell TJ, Helgeson K, Mauras N, 2001 Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects. J Clin Endocrinol Metab 86: 2211–2219.

    PubMed  CAS  Google Scholar 

  40. Stratikopoulos E, Szabolcs M, Dragatsis I, Klinakis A, Efstratiadis A, 2008 The hormonal action of IGF1 in postnatal mouse growth. Proc Natl Acad Sci U S A 105: 19378–19383.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Carroll PV, 1999 Protein metabolism and the use of growth hormone and insulin-like growth factor-I in the critically ill patient. Growth Horm IGF Res 9: 400–413.

    Article  PubMed  CAS  Google Scholar 

  42. Nakhjavani M, Esteghamati A, Hamidi S, et al, 2009 Changes in growth hormone and insulin-like growth factor-I levels in the acute stage after open heart surgery and at the time of discharge. Exp Clin Endocrinol Diabetes 117: 413–416.

    Article  PubMed  CAS  Google Scholar 

  43. Cotterill AM, Mendel P, Holly JM, et al, 1996 The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery. Clin Endocrinol (Oxf) 44: 91–101.

    Article  CAS  Google Scholar 

  44. Roth-Isigkeit A, Brechmann J, Dibbelt L, Sievers HH, Raasch W, Schmucker P, 1998 Persistent endocrine stress response in patients undergoing cardiac surgery. J Endocrinol Invest 21: 12–19.

    Article  PubMed  CAS  Google Scholar 

  45. Wallin MK, Sellden E, Eksborg S, Brismar K, 2007 Amino acid infusion during anesthesia attenuates the surgery induced decline in IGF-1 and diminishes the “diabetes of injury”. Nutr Metab (Lond) 4: 2.

    Article  CAS  Google Scholar 

  46. Wolf M, Bohm S, Brand M, Kreymann G, 1996 Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells. Eur J Endocrinol 135: 729–737.

    Article  PubMed  CAS  Google Scholar 

  47. Defalque D, Brandt N, Ketelslegers JM, Thissen JP, 1999 GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors. Am J Physiol 276: E565–572.

    PubMed  CAS  Google Scholar 

  48. Priego T, Granado M, Ibanez de Caceres I, Martin AI, Villanua MA, Lopez-Calderon A, 2003 Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats. J Endocrinol 179: 107–117.

    Article  PubMed  CAS  Google Scholar 

  49. Wilson K, Broadhurst C, Diver M, Jackson M, Mottram P, 2005 Plasma insulin growth factor-1 and incident delirium in older people. Int J Geriatr Psychiatry 20: 154–159.

    Article  PubMed  CAS  Google Scholar 

  50. Schauer PR, Sirinek KR, 1995 The laparoscopic approach reduces the endocrine response to elective cholecystectomy. Am Surg 61: 106–111.

    PubMed  CAS  Google Scholar 

  51. Bluthe RM, Kelley KW, Dantzer R, 2006 Effects of insulin-like growth factor-I on cytokine-induced sickness behavior in mice. Brain Behav Immun 20: 57–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Park SE, Dantzer R, Kelley KW, McCusker RH, 2011 Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice. J Neuroinflammation 8: 12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Bjarnason R, Wickelgren R, Hermansson M, Hammarqvist F, Carlsson B, Carlsson LM, 1998 Growth hormone treatment prevents the decrease in insulin-like growth factor I gene expression in patients undergoing abdominal surgery. J Clin Endocrinol Metab 83: 1566–1572.

    PubMed  CAS  Google Scholar 

  54. Brill KT, Weltman AL, Gentili A, et al, 2002 Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. J Clin Endocrinol Metab 87: 5649–5657.

    Article  PubMed  CAS  Google Scholar 

  55. Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A, 2001 Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 229: 141–162.

    Article  PubMed  CAS  Google Scholar 

  56. Bajpai A, Menon PS, 2006 Insulin like growth factors axis and growth disorders. Indian J Pediatr 73: 67–71.

    Article  PubMed  Google Scholar 

  57. Baxter RC, 2000 Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278: E967–976.

    Article  PubMed  CAS  Google Scholar 

  58. Baxter RC, Martin JL, Beniac VA, 1989 High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum. J Biol Chem 264: 11843–11848.

    PubMed  CAS  Google Scholar 

  59. Firth SM, Baxter RC, 2002 Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23: 824–854.

    Article  PubMed  CAS  Google Scholar 

  60. Martin RM, Holly JM, Davey Smith G, Gunnell D, 2006 Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort. J Clin Endocrinol Metab 91: 3287–3295.

    Article  PubMed  CAS  Google Scholar 

  61. Belizon A, Kirman I, Balik E, Karten M, Jain S, Whelan RL, 2007 Major surgical trauma induces proteolysis of insulin-like growth factor binding protein-3 in transgenic mice and is associated with a rapid increase in circulating levels of matrix metalloproteinase-9. Surg Endosc 21: 653–658.

    Article  PubMed  CAS  Google Scholar 

  62. Davenport ML, Isley WL, Pucilowska JB, et al, 1992 Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery. J Clin Endocrinol Metab 75: 590–595.

    PubMed  CAS  Google Scholar 

  63. Cwyfan Hughes SC, Cotterill AM, Molloy AR, et al, 1992 The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery. J Endocrinol 135: 135–145.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. 2nd Propaedeutic Department of Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Ag. Thoma 17, Goudi-Athens, 11527, Greece

    Themistoklis Floras MD, Dimitrios Bardakostas & Dimitrios Mantas

  2. Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Anastassios Philippou & Michael Koutsilieris

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  1. Themistoklis Floras MD
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  2. Anastassios Philippou
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  3. Dimitrios Bardakostas
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Correspondence to Themistoklis Floras MD.

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Floras, T., Philippou, A., Bardakostas, D. et al. The growth endocrine axis and inflammatory responses after laparoscopic cholecystectomy. Hormones 15, 73–80 (2016). https://doi.org/10.1007/BF03401405

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