Paraoxonase 1 Activity and Survival in Sepsis Patients

Yıl 2015, Cilt: 32 Sayı: 2, 183 - 188, 01.04.2015

Volkan İnal Levent Yamanel Gürhan Taşkın Serkan Tepen Bilgin Cömert

Öz

Background: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. Aims: The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. Study Design: Observational study. Methods: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-α and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients’ disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28th day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients’ survival. Results: In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-α (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were significantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol levels (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p<0.001 for all). TNF-α (r=-0.763) and IL-6 levels (r=-0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-α (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t:-16.489, p<0.001) were the most significant negative factor for survival, and TNF-α levels (t:-4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). Conclusion: The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival.

Anahtar Kelimeler

Mortality, paraoxonase 1, sepsis

Kaynakça

• 1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637. [CrossRef]
• 2. Galley HF. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth 2011;107:57-64. [CrossRef]
• 3. Pinsky MR. Dysregulation of the immune response in severe sepsis. Am J Med Sci 2004;328:220-9. [CrossRef]
• 4. Andrades ME, Ritter C, Dal-Pizzol F. The role of free radicals in sepsis development. Front Biosci (Elite Ed) 2009;1:277-87.
• 5. Draganov D, Teiber J, Watson C, Bisgaier C, Nemzek J, Remick D, et al. PON1 and oxidative stress in human sepsis and an animal model of sepsis. Adv Exp Med Biol 2010;660:89-97. [CrossRef]
• 6. Chien JY, Jerng JS, Yu CJ, Yang PC. Low serum level of highdensity lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 2005;33:1688-93. [CrossRef]
• 7. Bojic S, Kotur-Stevuljevic J, Kalezic N, Jelic-Ivanovic Z, Stefanovic A, Palibrk I, et al. Low paraoxonase 1 activity predicts mortality in surgical patients with sepsis. Dis Markers 2014;2014:427378. [CrossRef]
• 8. Li Y, Zhai R, Li H, Mei X, Qiu G. Prognostic value of serum paraoxonase and arylesterase activity in patients with sepsis. J Int Med Res 2013;41:681-7. [CrossRef]
• 9. Mackness B, Mackness M. Anti-inflammatory properties of paraoxonase-1 in atherosclerosis. Adv Exp Med Biol 2010;660:143- 51. [CrossRef]
• 10. Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res 2004;95:764-72. [CrossRef]
• 11. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29. [CrossRef]
• 12. Huen K, Richter R, Furlong C, Eskenazi B, Holland N. Validation of PON1 enzyme activity assays for longitudinal studies. Clinic Chimic Acta 2009;402:67-74. [CrossRef]
• 13. Barati M, Nazari MR, TalebiTaher M, Farhadi N. Comparison of Lipid Profile in Septic and Non-Septic Patients. Iran J Clin Infect Dis 2011;6:144-47.
• 14. Shor R, Wainstein J, Oz D, Boaz M, Matas Z, Fux A, et al. Low HDL levels and the risk of death, sepsis and malignancy. Clin Res Cardiol 2007;97:227-33. [CrossRef]
• 15. Barlage S, Gnewuch C, Liebisch G, Wolf Z, Audebert FX, Glück T, et al. Changes in HDL-associated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation. Intensive Care Med 2009;35:1877-85. [CrossRef]
• 16. Costa LG, Furlong CE. Paraoxonase (PON1) in health and disease: basic and clinical aspects. Ch.6. Protective action of HDLassociated PON1 against LDL oxidation, Ch.Ed; Navab M., Hama S.Y., Wagner A.C., Hough G., Watson A.D.), pp. 125-36. Norwell, MA: Kluwer Academic Publishers; 2002.
• 17. Feingold KR, Memon RA, Moser AH, Grunfeld C. Paraoxonase activity in the serum and hepatic mRNA levels decrease during the acute phase response. Atherosclerosis 1998;139:307-15. [CrossRef]
• 18. Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998;394:284-7. [CrossRef]
• 19. Novak F, Vavrova L, Kodydkova J, Sr FN, Hynkova M, Zak A, et al. Decreased paraoxonase activity in critically ill patients with sepsis. Clin Expe Med 2010;10:21-5. [CrossRef]