Abstract
Objective
Plasma concentrations of inflammatory mediators are substantially increased in major orthopaedic surgery. It was our hypothesis that corticosteroids would reduce the post-operative levels of inflammatory mediators in patients with ankylosing spondylitis, and we performed a single-centre randomised controlled trial.
Patients and methods
In 20 consecutive patients, an osteotomy of the lumbar spine was done. By concealed random allocation, 10 of the patients were given 10 mg/kg of methylprednisolone pre-operatively. The control patients received the same amount of saline. Samples of arterial blood and local blood from the surgical site were sampled and analysed for inflammatory cytokines and prostaglandin E2.
Results
There were significant increments in systemic levels of IL-6, IL-10 and sTNF-R1. Corticosteroids significantly reduced the increases of IL-6 and significantly increased the levels of IL-10 and sTNF-R1. Locally, the expressions of TNF-α, IL-1β, IL-6 and sTNF-R1 were significantly increased in both groups post-operatively. Corticosteroids significantly increased the local expressions of IL-10 and sTNF-R1. There were significantly higher local than systemic levels of inflammatory mediators except for TNF-α.
Conclusion
This study shows that in traumatic injury there are generally higher local than systemic expressions of inflammatory mediators, and that the main anti-inflammatory effects of high-dose corticosteroids are suppression of systemic IL-6 and increased expressions of IL-10 and sTNF-R1, both systemically and locally.
Similar content being viewed by others
References
Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;Suppl 3:iii8–iii18.
Keller C, Webb A, Davies J. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann Rheum Dis. 2003;62:1128–32.
Sonel B, Tutkak H, Duzgun N. Serum levels of Il-1 beta, TNF-alpha, Il-8, and acute phase proteins in seronegative spondyloarthropathies. Joint Bone Spine. 2002;69:463–8.
Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum. 1995;38:499–505.
Francois RJ, Neure L, Sieper J, Braun J. Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann Rheum Dis. 2006;65:713–20.
Lange U, Teichmann J, Stracke H. Correlation between plasma TNF-alpha, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity, and clinical manifestations in ankylosing spondylitis. Eur J Med Res. 2000;5:507–11.
Drouart M, Saas P, Billot M, Cedoz JP, Tiberghien P, Wendling D. High serum vascular endothelial growth factor correlates with disease activity of spondylarthropathies. Clin Exp Immunol. 2003;132:158–62.
Sieper J, Baraliakos X, Listing J, Brandt J, Haibel H, Rudwaleit M. Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 years of treatment with the anti-tumour necrosis factor agent infliximab. Rheumatology. 2005;44:1525–30.
Braun J, Landewe R, Hermann KG, Han J, Yan S, Williamson P. Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Arthritis Rheum. 2006;54:1646–52.
Visvanathan S, Wagner C, Marini JC, Baker D, Gathany T, Han J, et al. Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosisng spondylitis after treatment with infliximab. J Ann Rheum Dis. 2008;67:511–7.
Schleimer RP. An overview of glucocorticoid anti-inflammatory actions. Eur J Clin Pharmacol. 1993;45:S3–7.
Skjelbred P, Løkken P. Reduction of pain and swelling by a corticosteroid. Eur J Clin Pharmacol. 1982;21:391–6.
Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg. 2002;195:694–712.
Bisgaard T, Klarskov B, Kehlet H, Rosenberg J. Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy. A randomized double-blind placebo-controlled trial. Ann Surg. 2003;238:651–60.
Lundin A, Magnuson A, Axelsson K, Kogler H, Samuelsson L. The effect of perioperative corticosteroids on the outcome of microscopic lumbar disc surgery. Eur Spine J. 2003;12:625–30.
Ferreira SH, Cunha FQ, Lorenzetti FB. Role of lipocortin-1 in the anti-hyperalgesic actions of dexamethasone. Br J Pharmacol. 1997;121:883–8.
Baigrie RJ, Lamont PM, Kwiatkowski D, Dallman MJ, Morris PJ. Systemic cytokine response after major surgery. Br J Surg. 1992;79(8):757–60.
Garret S, Jenkins T, Kennedy LG. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21:2286–91.
Calin A, Garret S, Whitelock H. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994;21:2281–5.
Kennedy LG, Jenkinson TR, Mallorie PA, Whitelock HC, Barret SL, Calin A. Ankylosing spondylitis: the correlation between metrology score and radiology. Br J Rheumatol. 1995;34:767–71.
Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med. 1976;84:304–15.
Braun J, Bollow M, Seyrekbasan F, Häberle HJ, Eggens U, Mertz A, et al. Computed tomography guided corticosteroid injection of the sacroiliac joint in patients with spondyloarthropathy with sacroiliitis: clinical outcome and followup by dynamic magnetic resonance imaging. J Rheumatol. 1996;23:659–64.
af Klint E, Grundtman C, Engström M, Catrina AI, Makrygiannakis D, Klareskog L, et al. Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels. Arthritis Rheum. 2009;52:3880–9.
Youssef PP, Haynes DR, Triantafillou S, Parker A, Gamble JR, Roberts-Thomson PJ. Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis. Arthritis Rheum. 1997;40:1400–8.
Sauerland S, Nagelschmidt M, Mallmann P, Neugebeuer EA. Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review. Drug Saf. 2000;23:449–61.
Gilron I, Milne B, Hong M. Cyclooxygenase-2 inhibitors in postoperative pain management. Current evidence and future directions. Anesthesiology. 2003;99:1198–208.
Fereira SH, Lorenzetti BB, Poole S. Bradykinin initiates cytokine mediated inflammatory hyperalgesia. Br J Phamacol. 1993;110:127–31.
Baton BE, Jakaway JP, Smith SR, Siegel MI. Cytokine inhibition by a novel steroid, mometasone furoate. Immunopharmacol Immunotoxicol. 1991;13:251–61.
Liberman AC, Druker J, Perone MJ, Arzt E. Glucocorticoids in the regulation of transcription factors that control cytokine synthesis. Cytokine Growth Factor Rev. 2007;18:45–56.
Scheinman RI, Cogwell PC, Lofquist AK, Baldwin AS Jr. Role of transcriptional activation I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science. 1995;13(270):232–3.
Scheinman RI, Gualberto A, Jewll CM, Cidlowski JA, Baldwin AS. Characterization of mechanisms involved in transpression of NF-kappa B by activated glucoid receptors. Cell Mol Biol. 1995;15:943–53.
Adcock IM, Shirasaki H, Gelder CM. The effect of glucocorticoids on phorbol ester and cytokine stimulated transcription factor activation in human lung. Life Sci. 1994;55:1147–53.
Barnes PJ, Karin M. Mechanism of disease: nuclear factor-[kappa]B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;15:1066–71.
Krohn CD, Reikerås O, Aasen AO. The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble receptor I, and IL10 in drained and systemic blood after major orthopaedic surgery. Eur J Surg. 1999;165:101–9.
Clementsen T, Krohn CD, Reikerås O. Systemic and local cytokine patterns during total hip surgery. Scand J Clin Lab Invest. 2006;66:535–42.
Kotake S, Sato K, Kim KJ. Interleukin-6 and soluble interleukin-6 in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J Bone Miner Res. 1996;11:88–95.
Okamoto H, Yamamura M, Morita Y. The synovial expression and blood levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis Rheum. 1997;40:1096–105.
Steensberg A, Fischer CP, Keller C, Kirsten Møller, Pedersen BK. Il-6 enhances plasma Il-1ra, Il-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285:E433–7.
Waage A, Slupphaug G, Shalaby R. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur J Immunol. 1990;20:2439–43.
Fantuzzi G, Ghezzi P. Glucocorticoids as cytokine inhibitors: role in neuroendocrine control and therapy of inflammatory diseases. Mediators Inflamm. 1993;2:263–70.
Høgevold HE, Kierulf P, Ovstebø R, Reikerås O. Acute phase reactant and interleukin 6 after total hip replacement. Effects of high dose corticosteroids. Eur J Surg. 1992;158:339–45.
Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83:113–8.
Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth. 1997;78:201–19.
Ayala A, Lehman DL, Herdon CD, Chaudry IH. Mechanism of enhanced susceptibility to sepsis following hemorrhage: interleukin-10 suppression of T-cell response is mediated by eicosanoid-induced interleukin-4 release. Arch Surg. 1994;129:1172–8.
Barber AE, Coyle SM, Marano MA, Fischer E, Calvano SE, Fong Y, et al. Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol. 1993;150:1999–2006.
Dandona P, Aljada A, Garg R, Mohanty P. Increase in plasma Interleukin–10 following hydrocortisone injection. J Clin Endocinol Metab. 1999;84:1141–4.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible Editor: A. Bauhofer.
Rights and permissions
About this article
Cite this article
Reikerås, O., Helle, A., Krohn, C.D. et al. Effects of high-dose corticosteroids on post-traumatic inflammatory mediators. Inflamm. Res. 58, 891–897 (2009). https://doi.org/10.1007/s00011-009-0061-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-009-0061-3