Archives of Critical Care Medicine

Published by: Kowsar

New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients

Leonardo Lorente 1 , *
Author Information
1 Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Spain
Article information
  • Archives of Critical Care Medicine: May 28, 2015, 1 (2); e3125
  • Published Online: May 30, 2015
  • Article Type: Review Article
  • Received: March 1, 2015
  • Accepted: May 10, 2015
  • DOI: 10.17795/accm-3125

To Cite: Lorente L. New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients, Arch Crit Care Med. 2015 ; 1(2):e3125. doi: 10.17795/accm-3125.

Copyright © 2015, Shahid Beheshti University of Medical Siences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006; 34(2): 344-53[PubMed]
  • 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(7): 1303-10[PubMed]
  • 3. Andrades ME, Ritter C, Dal-Pizzol F. The role of free radicals in sepsis development. Front Biosci (Elite Ed). 2009; 1: 277-87[PubMed]
  • 4. Andrades ME, Morina A, Spasic S, Spasojevic I. Bench-to-bedside review: sepsis - from the redox point of view. Crit Care. 2011; 15(5): 230[DOI][PubMed]
  • 5. Rocha M, Herance R, Rovira S, Hernandez-Mijares A, Victor VM. Mitochondrial dysfunction and antioxidant therapy in sepsis. Infect Disord Drug Targets. 2012; 12(2): 161-78[PubMed]
  • 6. Galley HF. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011; 107(1): 57-64[DOI][PubMed]
  • 7. Galley HF. Bench-to-bedside review: Targeting antioxidants to mitochondria in sepsis. Crit Care. 2010; 14(4): 230[DOI][PubMed]
  • 8. Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 1990; 186: 421-31[PubMed]
  • 9. Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006; 52(4): 601-23[DOI][PubMed]
  • 10. Chuang CC, Shiesh SC, Chi CH, Tu YF, Hor LI, Shieh CC, et al. Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis. Crit Care. 2006; 10(1)[DOI][PubMed]
  • 11. Guerreiro MO, Petronilho F, Andrades M, Constantino L, Mina FG, Moreira JC, et al. Plasma superoxide dismutase activity and mortality in septic patients [corrected]. J Trauma. 2010; 69(6)-6[DOI][PubMed]
  • 12. Cowley HC, Bacon PJ, Goode HF, Webster NR, Jones JG, Menon DK. Plasma antioxidant potential in severe sepsis: a comparison of survivors and nonsurvivors. Crit Care Med. 1996; 24(7): 1179-83[PubMed]
  • 13. Ogilvie AC, Groeneveld AB, Straub JP, Thijs LG. Plasma lipid peroxides and antioxidants in human septic shock. Intensive Care Med. 1991; 17(1): 40-4[PubMed]
  • 14. Erdem SS, Yerlikaya FH, Cicekler H, Gul M. Association between ischemia-modified albumin, homocysteine, vitamin B(12) and folic acid in patients with severe sepsis. Clin Chem Lab Med. 2012; 50(8): 1417-21[DOI][PubMed]
  • 15. Gelain DP, de Bittencourt Pasquali MA, M. Comim C , Grunwald MS, Ritter C, Tomasi CD, et al. Serum heat shock protein 70 levels, oxidant status, and mortality in sepsis. Shock. 2011; 35(5): 466-70[DOI][PubMed]
  • 16. Andresen M, Regueira T, Bruhn A, Perez D, Strobel P, Dougnac A, et al. Lipoperoxidation and protein oxidative damage exhibit different kinetics during septic shock. Mediators Inflamm. 2008; 2008: 168652[DOI][PubMed]
  • 17. Toufekoula C, Papadakis V, Tsaganos T, Routsi C, Orfanos SE, Kotanidou A, et al. Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and clinical evidence. Crit Care. 2013; 17(1)[DOI][PubMed]
  • 18. 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(4): 646-51[PubMed]
  • 19. Lorente L, Martin MM, Abreu-Gonzalez P, Dominguez-Rodriguez A, Labarta L, Diaz C, et al. Prognostic value of malondialdehyde serum levels in severe sepsis: a multicenter study. PLoS One. 2013; 8(1)[DOI][PubMed]
  • 20. Lorente L, Martin MM, Abreu-Gonzalez P, Dominguez-Rodriguez A, Labarta L, Diaz C, et al. Sustained high serum malondialdehyde levels are associated with severity and mortality in septic patients. Crit Care. 2013; 17(6)[DOI][PubMed]
  • 21. Halliwell B, Cross CE. Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect. 1994; 102 Suppl 10: 5-12[PubMed]
  • 22. Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol. 2001; 54(3): 176-86[PubMed]
  • 23. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med. 2000; 29(11): 1106-14[PubMed]
  • 24. Cheng CH, Huang SC, Chiang TY, Wong Y, Huang YC. Higher plasma pyridoxal phosphate is associated with increased antioxidant enzyme activities in critically ill surgical patients. Biomed Res Int. 2013; 2013: 572081[DOI][PubMed]
  • 25. Alonso de Vega JM, Diaz J, Serrano E, Carbonell LF. Oxidative stress in critically ill patients with systemic inflammatory response syndrome. Crit Care Med. 2002; 30(8): 1782-6[PubMed]
  • 26. Dasgupta A, Malhotra D, Levy H, Marcadis D, Blackwell W, Johnston D. Decreased total antioxidant capacity but normal lipid hydroperoxide concentrations in sera of critically ill patients. Life Sci. 1997; 60(4-5): 335-40[PubMed]
  • 27. MacKinnon KL, Molnar Z, Lowe D, Watson ID, Shearer E. Measures of total free radical activity in critically ill patients. Clin Biochem. 1999; 32(4): 263-8[PubMed]
  • 28. Tsai K, Hsu T, Kong C, Lin K, Lu F. Is the endogenous peroxyl-radical scavenging capacity of plasma protective in systemic inflammatory disorders in humans? Free Radic Biol Med. 2000; 28(6): 926-33[PubMed]
  • 29. Karapetsa M, Pitsika M, Goutzourelas N, Stagos D, Tousia Becker A, Zakynthinos E. Oxidative status in ICU patients with septic shock. Food Chem Toxicol. 2013; 61: 106-11[DOI][PubMed]
  • 30. Doise JM, Aho LS, Quenot JP, Guilland JC, Zeller M, Vergely C, et al. Plasma antioxidant status in septic critically ill patients: a decrease over time. Fundam Clin Pharmacol. 2008; 22(2): 203-9[DOI][PubMed]
  • 31. Pascual C, Karzai W, Meier-Hellmann A, Oberhoffer M, Horn A, Bredle D, et al. Total plasma antioxidant capacity is not always decreased in sepsis. Crit Care Med. 1998; 26(4): 705-9[PubMed]
  • 32. Lorente L, Martin MM, Almeida T, Abreu-Gonzalez P, Ferreres J, Sole-Violan J, et al. Association between serum total antioxidant capacity and mortality in severe septic patients. J Crit Care. 2015; 30(1): 217 e7-12[DOI][PubMed]
  • 33. Cagnacci A. Melatonin in relation to physiology in adult humans. J Pineal Res. 1996; 21(4): 200-13[PubMed]
  • 34. Dawson D, Encel N. Melatonin and sleep in humans. J Pineal Res. 1993; 15(1): 1-12[PubMed]
  • 35. Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res. 2011; 51(1): 1-16[DOI][PubMed]
  • 36. Mauriz JL, Collado PS, Veneroso C, Reiter RJ, Gonzalez-Gallego J. A review of the molecular aspects of melatonin's anti-inflammatory actions: recent insights and new perspectives. J Pineal Res. 2013; 54(1): 1-14[DOI][PubMed]
  • 37. Kurdi MS, Patel T. The role of melatonin in anaesthesia and critical care. Indian J Anaesth. 2013; 57(2): 137-44[DOI][PubMed]
  • 38. Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med. 2006; 32(3): 371-9[DOI][PubMed]
  • 39. Reiter RJ, Paredes SD, Manchester LC, Tan DX. Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin. Crit Rev Biochem Mol Biol. 2009; 44(4): 175-200[DOI][PubMed]
  • 40. Srinivasan V, Mohamed M, Kato H. Melatonin in bacterial and viral infections with focus on sepsis: a review. Recent Pat Endocr Metab Immune Drug Discov. 2012; 6(1): 30-9[PubMed]
  • 41. Srinivasan V, Pandi-Perumal SR, Spence DW, Kato H, Cardinali DP. Melatonin in septic shock: some recent concepts. J Crit Care. 2010; 25(4): 656 e1-6[DOI][PubMed]
  • 42. Escames G, Acuna-Castroviejo D, Lopez LC, Tan DX, Maldonado MD, Sanchez-Hidalgo M, et al. Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence. J Pharm Pharmacol. 2006; 58(9): 1153-65[DOI][PubMed]
  • 43. Rinaldi S, Landucci F, De Gaudio AR. Antioxidant therapy in critically septic patients. Curr Drug Targets. 2009; 10(9): 872-80[PubMed]
  • 44. Verceles AC, Silhan L, Terrin M, Netzer G, Shanholtz C, Scharf SM. Circadian rhythm disruption in severe sepsis: the effect of ambient light on urinary 6-sulfatoxymelatonin secretion. Intensive Care Med. 2012; 38(5): 804-10[DOI][PubMed]
  • 45. Li CX, Liang DD, Xie GH, Cheng BL, Chen QX, Wu SJ, et al. Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients. Mol Med Rep. 2013; 7(4): 1117-22[DOI][PubMed]
  • 46. Mundigler G, Delle-Karth G, Koreny M, Zehetgruber M, Steindl-Munda P, Marktl W, et al. Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med. 2002; 30(3): 536-40[PubMed]
  • 47. Bagci S, Horoz OO, Yildizdas D, Reinsberg J, Bartmann P, Muller A. Melatonin status in pediatric intensive care patients with sepsis. Pediatr Crit Care Med. 2012; 13(2)-3[DOI][PubMed]
  • 48. Perras B, Kurowski V, Dodt C. Nocturnal melatonin concentration is correlated with illness severity in patients with septic disease. Intensive Care Med. 2006; 32(4): 624-5[DOI][PubMed]
  • 49. Alamili M, Bendtzen K, Lykkesfeldt J, Rosenberg J, Gogenur I. Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model. J Crit Care. 2014; 29(1): 184 e9-184 e13[DOI][PubMed]
  • 50. Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, et al. Effects of melatonin treatment in septic newborns. Pediatr Res. 2001; 50(6): 756-60[DOI][PubMed]
  • 51. Lorente L, Martin MM, Abreu-Gonzalez P, de la Cruz T, Ferreres J, Sole-Violan J, et al. Serum melatonin levels are associated with mortality in severe septic patients. J Crit Care. 2015; 30(4): 860 e1-6[DOI][PubMed]
  • 52. Xing HY, Ling YL, Meng AH, Zhao XY, Huang XL. [Melatonin improves vascular reactivity of endotoxemia rats]. Sheng Li Xue Bao. 2005; 57(3): 367-72[PubMed]
  • 53. Sener G, Toklu H, Kapucu C, Ercan F, Erkanli G, Kacmaz A, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today. 2005; 35(1): 52-9[DOI][PubMed]
  • 54. Paskaloglu K, Sener G, Kapucu C, Ayanoglu-Dulger G. Melatonin treatment protects against sepsis-induced functional and biochemical changes in rat ileum and urinary bladder. Life Sci. 2004; 74(9): 1093-104[PubMed]
  • 55. Ortiz F, Garcia JA, Acuna-Castroviejo D, Doerrier C, Lopez A, Venegas C, et al. The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res. 2014; 56(1): 71-81[DOI][PubMed]
  • 56. Wu JY, Tsou MY, Chen TH, Chen SJ, Tsao CM, Wu CC. Therapeutic effects of melatonin on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats. J Pineal Res. 2008; 45(1): 106-16[DOI][PubMed]
  • 57. Carrillo-Vico A, Lardone PJ, Naji L, Fernandez-Santos JM, Martin-Lacave I, Guerrero JM, et al. Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in mice: regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res. 2005; 39(4): 400-8[DOI][PubMed]
  • 58. Martin M, Macias M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, et al. Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res. 2000; 28(4): 242-8[PubMed]
  • 59. Lowes DA, Webster NR, Murphy MP, Galley HF. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth. 2013; 110(3): 472-80[DOI][PubMed]
  • 60. Fink T, Glas M, Wolf A, Kleber A, Reus E, Wolff M, et al. Melatonin receptors mediate improvements of survival in a model of polymicrobial sepsis. Crit Care Med. 2014; 42(1)-31[DOI][PubMed]
  • 61. Fulia F, Gitto E, Cuzzocrea S, Reiter RJ, Dugo L, Gitto P, et al. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: reduction by melatonin. J Pineal Res. 2001; 31(4): 343-9[PubMed]
  • 62. Sahib AS, Al-Jawad FH, Alkaisy AA. Effect of antioxidants on the incidence of wound infection in burn patients. Ann Burns Fire Disasters. 2010; 23(4): 199-205[PubMed]
  • 63. Fink M. Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl. 1997; 110: 87-95[PubMed]
  • 64. Boekstegers P, Weidenhofer S, Pilz G, Werdan K. Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection. 1991; 19(5): 317-23[PubMed]
  • 65. Sair M, Etherington PJ, Peter Winlove C, Evans TW. Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med. 2001; 29(7): 1343-9[PubMed]
  • 66. Hayes MA, Timmins AC, Yau EH, Palazzo M, Watson D, Hinds CJ. Oxygen transport patterns in patients with sepsis syndrome or septic shock: influence of treatment and relationship to outcome. Crit Care Med. 1997; 25(6): 926-36[PubMed]
  • 67. Sjovall F, Morota S, Asander Frostner E, Hansson MJ, Elmer E. Cytokine and nitric oxide levels in patients with sepsis--temporal evolvement and relation to platelet mitochondrial respiratory function. PLoS One. 2014; 9(5)[DOI][PubMed]
  • 68. Protti A, Fortunato F, Caspani ML, Pluderi M, Lucchini V, Grimoldi N, et al. Mitochondrial changes in platelets are not related to those in skeletal muscle during human septic shock. PLoS One. 2014; 9(5)[DOI][PubMed]
  • 69. Grundler K, Angstwurm M, Hilge R, Baumann P, Annecke T, Crispin A, et al. Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome. Crit Care. 2014; 18(1)[DOI][PubMed]
  • 70. Yamakawa K, Ogura H, Koh T, Ogawa Y, Matsumoto N, Kuwagata Y, et al. Platelet mitochondrial membrane potential correlates with severity in patients with systemic inflammatory response syndrome. J Trauma Acute Care Surg. 2013; 74(2): 411-7[DOI][PubMed]
  • 71. Sjovall F, Morota S, Hansson MJ, Friberg H, Gnaiger E, Elmer E. Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis. Crit Care. 2010; 14(6)[DOI][PubMed]
  • 72. Sjovall F, Morota S, Persson J, Hansson MJ, Elmer E. Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells. Crit Care. 2013; 17(4)[DOI][PubMed]
  • 73. Japiassu AM, Santiago AP, d'Avila JC, Garcia-Souza LF, Galina A, Castro Faria-Neto HC, et al. Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5'-triphosphate synthase activity. Crit Care Med. 2011; 39(5): 1056-63[DOI][PubMed]
  • 74. Garrabou G, Moren C, Lopez S, Tobias E, Cardellach F, Miro O, et al. The effects of sepsis on mitochondria. J Infect Dis. 2012; 205(3): 392-400[DOI][PubMed]
  • 75. Belikova I, Lukaszewicz AC, Faivre V, Damoisel C, Singer M, Payen D. Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. Crit Care Med. 2007; 35(12): 2702-8[PubMed]
  • 76. Adrie C, Bachelet M, Vayssier-Taussat M, Russo-Marie F, Bouchaert I, Adib-Conquy M, et al. Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis. Am J Respir Crit Care Med. 2001; 164(3): 389-95[DOI][PubMed]
  • 77. Carre JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, et al. Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med. 2010; 182(6): 745-51[DOI][PubMed]
  • 78. Fredriksson K, Tjader I, Keller P, Petrovic N, Ahlman B, Scheele C, et al. Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure. PLoS One. 2008; 3(11)[DOI][PubMed]
  • 79. Fredriksson K, Hammarqvist F, Strigard K, Hultenby K, Ljungqvist O, Wernerman J, et al. Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure. Am J Physiol Endocrinol Metab. 2006; 291(5)-50[DOI][PubMed]
  • 80. Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002; 360(9328): 219-23[DOI][PubMed]
  • 81. Gasparetto A, Corbucci GG, Candiani A, Gohil K, Edwards RH. Effect of tissue hypoxia and septic shock on human skeletal muscle mitochondria. Lancet. 1983; 2(8365-66): 1486[PubMed]
  • 82. Poderoso JJ, Boveris A, Jorge MA, Gherardi CR, Caprile AW, Turrens J, et al. [Mitochondrial function in septic shock]. Medicina (B Aires). 1978; 38(4): 371-7[PubMed]
  • 83. Lorente L, Martin MM, Lopez-Gallardo E, Iceta R, Sole-Violan J, Blanquer J, et al. Platelet cytochrome c oxidase activity and quantity in septic patients. Crit Care Med. 2011; 39(6): 1289-94[DOI][PubMed]
  • 84. Lorente L, Martin MM, Lopez-Gallardo E, Iceta R, Blanquer J, Sole-Violan J, et al. Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients. Crit Care. 2014; 18(3)[DOI][PubMed]
  • 85. Lorente L, Martin MM, Lopez-Gallardo E, Blanquer J, Sole-Violan J, Labarta L, et al. Decrease of oxidative phosphorylation system function in severe septic patients. J Crit Care. 2015; [DOI][PubMed]
  • 86. Piel DA, Gruber PJ, Weinheimer CJ, Courtois MR, Robertson CM, Coopersmith CM, et al. Mitochondrial resuscitation with exogenous cytochrome c in the septic heart. Crit Care Med. 2007; 35(9): 2120-7[PubMed]
  • 87. Piel DA, Deutschman CS, Levy RJ. Exogenous cytochrome C restores myocardial cytochrome oxidase activity into the late phase of sepsis. Shock. 2008; 29(5): 612-6[DOI][PubMed]
  • 88. Verma R, Huang Z, Deutschman CS, Levy RJ. Caffeine restores myocardial cytochrome oxidase activity and improves cardiac function during sepsis. Crit Care Med. 2009; 37(4): 1397-402[DOI][PubMed]
  • 89. Groening P, Huang Z, La Gamma EF, Levy RJ. Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis. JPEN J Parenter Enteral Nutr. 2011; 35(2): 249-54[DOI][PubMed]
  • 90. Yang Y, Shou Z, Zhang P, He Q, Xiao H, Xu Y, et al. Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population. Genet Med. 2008; 10(3): 187-92[DOI][PubMed]
  • 91. Baudouin SV, Saunders D, Tiangyou W, Elson JL, Poynter J, Pyle A, et al. Mitochondrial DNA and survival after sepsis: a prospective study. Lancet. 2005; 366(9503): 2118-21[DOI][PubMed]
  • 92. Lorente L, Iceta R, Martin MM, Lopez-Gallardo E, Sole-Violan J, Blanquer J, et al. Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup. Crit Care. 2012; 16(1)[DOI][PubMed]
  • 93. Lorente L, Iceta R, Martin MM, Lopez-Gallardo E, Sole-Violan J, Blanquer J, et al. Severe septic patients with mitochondrial DNA haplogroup JT show higher survival rates: a prospective, multicenter, observational study. PLoS One. 2013; 8(9)[DOI][PubMed]
  • 94. Bellizzi D, Cavalcante P, Taverna D, Rose G, Passarino G, Salvioli S, et al. Gene expression of cytokines and cytokine receptors is modulated by the common variability of the mitochondrial DNA in cybrid cell lines. Genes Cells. 2006; 11(8): 883-91[DOI][PubMed]
  • 95. Hack CE, De Groot ER, Felt-Bersma RJ, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ, et al. Increased plasma levels of interleukin-6 in sepsis. Blood. 1989; 74(5): 1704-10[PubMed]
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