DYNAMICS OF SYSTEMIC INFLAMMATORY RESPONSE MARKERS IN PATIENTS WITH URGENT CONDITIONS DEPEND-ING ON THE DEVELOPMENT OF SEPSIS

Background There is still no information on the dynamics of pro- and anti-inflammatory cytokines and mark-ers of the septic process before the clinical manifestation of sepsis. The aim of the study was to analyze the dynamics of inflammation and sepsis markers concentration in early periods in patients with urgent pathology, depending on the subsequently developed sepsis. Materials and methods. The concentration of procalcitonin, C-reactive protein, LBP, IL-6, IL-10, IL-2R in 61 patients with a high risk of sepsis was investigated starting from the first day after admission to the hospital and then with intervals of 3–5 days. The Group 1 included 29 patients with verified sepsis. All patients of this group survived. The Group 2 included 8 patients who died. The Group 3 included 24 patients who had no clinical signs of sepsis. All the patients in this group recovered. Results. We revealed significant differences in concentrations of systemic inflammatory response markers and its dynamics in the period preceding clinical manifestations of sepsis. It was found that it was possible to predict the development of sepsis and its unfavorable outcome with a high statistical probability in the study of paired samples of blood serum of patients received on day 1–3 and 4–6 from the onset of the disease or severe trauma. The predictors were multidirectional changes of IL-6, IL-10, LBP concentrations and more than three-fold IL-2R increase on the background of high concentrations of procalcitonin and C-reactive protein. Conclusion. The highest concentrations of procalcitonin, C-reactive protein, IL-10 and IL-2R were revealed within the first three days in patients who died of sepsis. High concentrations of IL-6 and IL-10 within first three days and different directions of their concentrations during the next 4–6 days indicate the development of sepsis with an unfavorable outcome. Reduction of IL-2R and IL-6 and an increase in IL-10 within the first week after the onset of the disease or trau-ma are predictors of lethal outcome.

1. Gaini S., Koldkjaer O.G., Pedersen C., Pedersen S.S. Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study. Crit Care. 2006; 10(2): R53. PMID: 16569262. PMCID: PMC1550885. DOI: 10.1186/cc4866

2. Heper Y, Akalin E.H., Mistik R., et al. Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock. Eur J Clin Microbiol Infect Dis. 2006; 25(8): 481–491. PMID: 16896829. DOI: 10.1007/s10096-006-0168-1.

3. Maier B., Lefering R., Lehnert M., et al. Early versus late onset of multiple organ failure is associated with differing patterns of plasma cytokine biomarker expression and outcome after severe trauma. Shock. 2007; 28(6): 668–674. PMID: 18092384.

4. Singer M., Deutschman C.S., Seymour Ch.W., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8): 801–810. PMID: 26903338. PMCID: PMC4968574. DOI:10.1001/jama.2016.0287

5. DeLong W.G. Jr., Born C.T. Cytokines in Patients with Polytrauma. Clin Orthop Relat Res. 2004; 422: 57–65. PMID: 15187834

6. Bulava G.V., Androsova M.V., Shabanov A.K., et al. Predictors of sepsis in patients with urgent conditions. Sklifosovsky Journal Emergency Medical Care. 2017; 6(1): 13–19. DOI:10.23934/2223-9022-2017-6-1- 13-19 (In Russian).

7. Zweigner J., Gramm H.J., Singer O.C., et al. High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes. Blood. 2001; 98(13): 3800–3808. PMID: 11739189.

8. Remick D.G., Bolgos G.R., Siddiqui J., et al. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock. 2002; 17: 463–467. PMID:12069181.

9. Kozlov V.K. Sepsis: etiology, immunopathogenesis, the concept of modern immunotherapy. Saint Petersburg: Dialekt Publ., 2006. 304 p. (In Russian).

10. Frink M., van Griensven M., Kobbe Ph., et al. IL-6 predicts organ dysfunction and mortality in patients with multiple injuries. Scand. J Trauma Resusc Emerg Med. 2009; 17: 49. PMID: 19781105. PMCID: PMC2763001. DOI: 10.1186/1757-7241-17-49.

11. Miyaoka K., Iwase M., Suzuki R., et al. Clinical evaluation of circulating interleukin-6 and interleukin-10 levels after surgery-induced inflammation. J Surg Res. 2005; 125 (2): 144–150. PMID: 15854666. DOI: 10.1016/j.jss.2004.12.001.

12. Manley M.O., O’Riordan M.A., Levine A.D., Latifi S.Q. Interleukin 10 extends the effectiveness of standard therapy during late sepsis with serum interleukin 6 levels predicting outcome. Shock. 2005; 23(6): 521–526. PMID: 15897804.

13. Rubin L.A., Nelson D.L. The soluble interleukin-2 receptor: Biology, function, and clinical application. Ann Intern Med. 1990; 113: 619–627. PMID: 2205142.

14. Ostanin O.A., Leplina O.Yu., Shevela E.Ya., at al. The assessment of cytokine pattern in patients with severe sepsis using the Bio/Plex/ protein assay system. Tsitokiny i vospalenie. 2004; 3(1): 20–27. (In Russian).

15. Anisimova N.Yu., Gromova E.G., Kuznetsova L.S., Kiselevskiy M.V. Prognosticheskoe znachenie syvorotochnogo urovnya lipopolisakharida i lipopolisakharid-svyazyvayushchego belka u onkologicheskikh bol’nykh s sepsisom. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2011; (2): 82–84. (In Russian).

16. Prucha M., Herold I., Zazula R., et al. Significance of lipopolysaccharidebinding protein (an acute phase protein) in monitoring critically ill patients. Crit Care Med. 2003; 7(6): R154–159. PMID: 14624690. PMCID: PMC374378. DOI: 10.1186/cc2386.

17. Sakran J.V., Michetti C.P., Sheridan M.J., et al. The utility of procalcitonin in critically ill trauma patients. J Trauma Acute Care Surg. 2012; 73(2): 413–418. PMID: 22846948. DOI: 10.1097/TA.0b013e31825ff5b7.

18. Reinhart K., Meisner M. Biomarkers in the critically ill patient: procalcitonin. Crit Care Clin. 2011; 27(2): 253–263. PMID: 21440200. DOI: 10.1016/j.ccc.2011.01.002.

19. Lobo S.M., Lobo F.R., Bota D.P., et al. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003; 123(6): 2043–2049. PMID: 12796187.