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Increased inflammatory markers with altered antioxidant status persist after clinical recovery from severe sepsis: a correlation with low HDL cholesterol and albumin

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Abstract

Markers of oxidative stress and antioxidant status in relation to inflammatory mediators in septic patients (SPs) during the course of sepsis and after recovery were analysed. Patients were 30 critically ill adults in severe sepsis/septic shock, 19 of which completed 3 samplings (S1: within 24 h after onset of sepsis, S7: 7 days after S1, R7: 7 days after clinical recovery). Comparing SPs with healthy controls (HCs), enhanced C-reactive protein, procalcitonin, bilirubin and CuZn-superoxide dismutase activity were found at S1 only. Oxidized low-density lipoprotein, conjugated dienes and nitrotyrosine were increased at S1, culminated at S7 and reverted nearly to HC levels at R7. Reduced catalase activity and serum amyloid were observed at S1 and endured until R7. Increase in IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) with accompanying decrease in apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, selenium, zinc, albumin, paraoxonase 1 and glutathione peroxidase 1 activity appeared at S1 and persisted until R7. TNF-α, IL-10 and markers of oxidative stress were in negative correlation with HDL cholesterol and albumin at R7. After clinical recovery, increased cytokines and decreased antioxidants were accompanied by lower albumin and HDL cholesterol levels. During this important and beneficial period of tissue repair, patients with prolonged persistence of this status are probably more vulnerable to secondary infections and should be dealt with as constituting a high-risk population.

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References

  1. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–6.

    Article  PubMed  Google Scholar 

  2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.

    Article  CAS  PubMed  Google Scholar 

  3. van Ruler O, Schultz MJ, Reitsma JB, Gouma DJ, Boermeester MA. Has mortality from sepsis improved and what to expect from new treatment modalities: review of current insights. Surg Infect (Larchmt). 2009;10:339–48.

    Article  Google Scholar 

  4. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14:R15.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348:138–50.

    Article  CAS  PubMed  Google Scholar 

  6. Gullo A, Bianco N, Berlot G. Management of severe sepsis and septic shock: challenges and recommendations. Crit Care Clin. 2006;22:489–501.

    Article  PubMed  Google Scholar 

  7. Frazier WJ, Hall MW. Immunoparalysis and adverse outcomes from critical illness. Pediatr Clin North Am. 2008;55:647–68.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29:617–25.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Crimi E, Sica V, Williams-Ignarro S, et al. The role of oxidative stress in adult critical care. Free Radic Biol Med. 2006;40:398–406.

    Article  CAS  PubMed  Google Scholar 

  10. Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med. 1995;23:646–51.

    Article  CAS  PubMed  Google Scholar 

  11. Bozza FA, Salluh JI, Japiassu AM, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 2007;11:R49.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Linner A, Sunden-Cullberg J, Johansson L, Hjelmqvist H, Norrby-Teglund A, Treutiger CJ. Short- and long-term mortality in severe sepsis/septic shock in a setting with low antibiotic resistance: a prospective observational study in a Swedish university hospital. Front Public Health. 2013;1:51.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lichtenstern C, Brenner T, Bardenheuer HJ, Weigand MA. Predictors of survival in sepsis: what is the best inflammatory marker to measure? Curr Opin Infect Dis. 2012;25:328–36.

    Article  CAS  PubMed  Google Scholar 

  15. Yende S, D’Angelo G, Kellum JA, et al. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008;177:1242–7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296–327.

    Article  PubMed  Google Scholar 

  17. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286:1754–8.

    Article  CAS  PubMed  Google Scholar 

  18. Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet. 1983;35:1126–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kodydkova J, Vavrova L, Zeman M, et al. Antioxidative enzymes and increased oxidative stress in depressive women. Clin Biochem. 2009;42:1368–74.

    Article  CAS  PubMed  Google Scholar 

  20. Ahotupa M, Ruutu M, Mantyla E. Simple methods of quantifying oxidation products and antioxidant potential of low density lipoproteins. Clin Biochem. 1996;29:139–44.

    Article  CAS  PubMed  Google Scholar 

  21. Guevara I, Iwanejko J, Dembinska-Kiec A, et al. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta. 1998;274:177–88.

    Article  CAS  PubMed  Google Scholar 

  22. Lasanianos NG, Kanakaris NK, Dimitriou R, Pape HC, Giannoudis PV. Second hit phenomenon: existing evidence of clinical implications. Injury. 2011;42:617–29.

    Article  CAS  PubMed  Google Scholar 

  23. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000;181:176–80.

    Article  CAS  PubMed  Google Scholar 

  24. Taniguchi T, Koido Y, Aiboshi J, Yamashita T, Suzaki S, Kurokawa A. Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med. 1999;27:1262–4.

    Article  CAS  PubMed  Google Scholar 

  25. Sethu S, Melendez AJ. New developments on the TNFalpha-mediated signalling pathways. Biosci Rep. 2011;31:63–76.

    Article  CAS  PubMed  Google Scholar 

  26. Huang ZF, Massey JB, Via DP. Differential regulation of cyclooxygenase-2 (COX-2) mRNA stability by interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in human in vitro differentiated macrophages. Biochem Pharmacol. 2000;59:187–94.

    Article  CAS  PubMed  Google Scholar 

  27. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510:92–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011;66(Suppl 2):33–40.

    Google Scholar 

  29. Behnes M, Brueckmann M, Liebe V, et al. Levels of oxidized low-density lipoproteins are increased in patients with severe sepsis. J Crit Care. 2008;23:537–41.

    Article  CAS  PubMed  Google Scholar 

  30. Baron P, Traber LD, Traber DL, et al. Gut failure and translocation following burn and sepsis. J Surg Res. 1994;57:197–204.

    Article  CAS  PubMed  Google Scholar 

  31. Andresen M, Regueira T, Bruhn A, et al. Lipoperoxidation and protein oxidative damage exhibit different kinetics during septic shock. Mediators Inflamm. 2008;2008:168652.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Strand OA, Leone A, Giercksky KE, Kirkeboen KA. Nitric oxide indices in human septic shock. Crit Care Med. 2000;28:2779–85.

    Article  CAS  PubMed  Google Scholar 

  33. Warner A, Bencosme A, Healy D, Verme C. Prognostic role of antioxidant enzymes in sepsis: preliminary assessment. Clin Chem. 1995;41:867–71.

    CAS  PubMed  Google Scholar 

  34. Cherian S, Jameson S, Rajarajeswari C, et al. Oxidative stress in sepsis in children. Indian J Med Res. 2007;125:143–8.

    CAS  PubMed  Google Scholar 

  35. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 4th edn. New York: Oxford University Press Inc.; 2007. p. 123–124, 347–348.

  36. Taylor DE, Piantadosi CA. Oxidative metabolism in sepsis and sepsis syndrome. J Crit Care. 1995;10:122–35.

    Article  CAS  PubMed  Google Scholar 

  37. Bulger EM, Maier RV. Antioxidants in critical illness. Arch Surg. 2001;136:1201–7.

    Article  CAS  PubMed  Google Scholar 

  38. Leff JA, Parsons PE, Day CE, et al. Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1992;146:985–9.

    Article  CAS  PubMed  Google Scholar 

  39. Andersen HR, Nielsen JB, Nielsen F, Grandjean P. Antioxidative enzyme activities in human erythrocytes. Clin Chem. 1997;43:562–8.

    CAS  PubMed  Google Scholar 

  40. Ding L, Liu Z, Zhu Z, Luo G, Zhao D, Ni J. Biochemical characterization of selenium-containing catalytic antibody as a cytosolic glutathione peroxidase mimic. Biochem J. 1998;332(Pt 1):251–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Forceville X, Vitoux D, Gauzit R, Combes A, Lahilaire P, Chappuis P. Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med. 1998;26:1536–44.

    Article  CAS  PubMed  Google Scholar 

  42. Mills GC. Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. J Biol Chem. 1957;229:189–97.

    CAS  PubMed  Google Scholar 

  43. Ogilvie AC, Groeneveld AB, Straub JP, Thijs LG. Plasma lipid peroxides and antioxidants in human septic shock. Intensive Care Med. 1991;17:40–4.

    Article  CAS  PubMed  Google Scholar 

  44. Weber SU, Lehmann LE, Schewe JC, et al. Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis. BioFactors. 2008;33:107–19.

    Article  CAS  PubMed  Google Scholar 

  45. Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol. 2001;54:176–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg. 1999;134:36–42.

    Article  CAS  PubMed  Google Scholar 

  47. Kragh-Hansen U, Minchiotti L, Galliano M, Peters T Jr. Human serum albumin isoforms: genetic and molecular aspects and functional consequences. Biochim Biophys Acta. 2013;1830:5405–17.

    Article  CAS  PubMed  Google Scholar 

  48. Evans TW. Review article: albumin as a drug–biological effects of albumin unrelated to oncotic pressure. Aliment Pharmacol Ther. 2002;16(Suppl 5):6–11.

    Article  CAS  PubMed  Google Scholar 

  49. Chiarla C, Giovannini I, Giuliante F, et al. Severe hypocholesterolemia in surgical patients, sepsis, and critical illness. J Crit Care. 2010;25:361.

    Article  PubMed  Google Scholar 

  50. van Leeuwen HJ, Heezius EC, Dallinga GM, van Strijp JA, Verhoef J, van Kessel KP. Lipoprotein metabolism in patients with severe sepsis. Crit Care Med. 2003;31:1359–66.

    Article  PubMed  Google Scholar 

  51. Tabet F, Rye KA. High-density lipoproteins, inflammation and oxidative stress. Clin Sci (Lond). 2009;116:87–98.

    Article  CAS  PubMed  Google Scholar 

  52. Gordon BR, Parker TS, Levine DM, et al. Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients. Crit Care Med. 2001;29:1563–8.

    Article  CAS  PubMed  Google Scholar 

  53. Luthold S, Berneis K, Bady P, Muller B. Effects of infectious disease on plasma lipids and their diagnostic significance in critical illness. Eur J Clin Invest. 2007;37:573–9.

    Article  CAS  PubMed  Google Scholar 

  54. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.

    Article  CAS  PubMed  Google Scholar 

  55. Marsche G, Saemann MD, Heinemann A, Holzer M. Inflammation alters HDL composition and function: implications for HDL-raising therapies. Pharmacol Ther. 2013;137:341–51.

    Article  CAS  PubMed  Google Scholar 

  56. Mackness B, Hine D, McElduff P, Mackness M. High C-reactive protein and low paraoxonase1 in diabetes as risk factors for coronary heart disease. Atherosclerosis. 2006;186:396–401.

    Article  CAS  PubMed  Google Scholar 

  57. Precourt LP, Amre D, Denis MC, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011;214:20–36.

    Article  CAS  PubMed  Google Scholar 

  58. Novak F, Vavrova L, Kodydkova J, et al. Decreased paraoxonase activity in critically ill patients with sepsis. Clin Exp Med. 2010;10:21–5.

    Article  CAS  PubMed  Google Scholar 

  59. Kedage V, Muttigi MS, Shetty MS, et al. Serum paraoxonase 1 activity status in patients with liver disorders. Saudi J Gastroenterol. 2010;16:79–83.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Draganov D, Teiber J, Watson C, et al. PON1 and oxidative stress in human sepsis and an animal model of sepsis. Adv Exp Med Biol. 2010;660:89–97.

    Article  CAS  PubMed  Google Scholar 

  61. Aviram M, Rosenblat M, Billecke S, et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999;26:892–904.

    Article  CAS  PubMed  Google Scholar 

  62. Garner B, Waldeck AR, Witting PK, Rye KA, Stocker R. Oxidation of high density lipoproteins. II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII. J Biol Chem. 1998;273:6088–95.

    Article  CAS  PubMed  Google Scholar 

  63. James RW, Deakin SP. The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity. Free Radic Biol Med. 2004;37:1986–94.

    Article  CAS  PubMed  Google Scholar 

  64. McGillicuddy FC, de la Llera MM, Hinkle CC, et al. Inflammation impairs reverse cholesterol transport in vivo. Circulation. 2009;119:1135–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sammalkorpi K, Valtonen V, Kerttula Y, Nikkila E, Taskinen MR. Changes in serum lipoprotein pattern induced by acute infections. Metabolism. 1988;37:859–65.

    Article  CAS  PubMed  Google Scholar 

  66. Gallin JI, Kaye D, O’Leary WM. Serum lipids in infection. N Engl J Med. 1969;281:1081–6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a research grant from the Ministry of Health of the Czech Republic (Project No. IGA NT/13236-4/2012).

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Correspondence to Frantisek Novak.

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Vavrova, L., Rychlikova, J., Mrackova, M. et al. Increased inflammatory markers with altered antioxidant status persist after clinical recovery from severe sepsis: a correlation with low HDL cholesterol and albumin. Clin Exp Med 16, 557–569 (2016). https://doi.org/10.1007/s10238-015-0390-1

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