Biomarkers of early sepsis may be correlated with outcome

Journal of Translational Medicine

Yih-Sharng Chen³  Sun-Liang Yu⁴  Chun-Ta Huang¹  Lu-Ping Chow⁵  Heng-Hsiu Liu²  Ching-Feng Lin²  Wen-Je Ko¹  Chin-Hao Chang⁶  Tsai-Hsia Hong³ 

[1]Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan

[2]Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

[3]Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan

[4]Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan

[5]Department of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan

[6]Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

关键词: Severe sepsis;    IL-10;    IL-8;    IL-6;    MCP-1;   

Others  :  810948
DOI  :  10.1186/1479-5876-12-146

 received in 2013-10-19, accepted in 2014-05-14,  发布年份 2014

【 摘 要 】

Background

Sepsis causes high mortality, and the mortality due to secondary infections is even higher. No studies to date have investigated the time from the primary infection to death due to a secondary infection; similarly, the factors that are significantly different in sepsis survivors relative to non-survivors or in severe sepsis patients who suffered a late death relative to those who recover have not been explored. We hypothesized that patients who survive sepsis have a weaker pro-inflammatory response than those who do not and that the mid-term survivors (which acquire secondary infections) would have a pronounced anti-inflammatory response (making them susceptible to infection); this hypothesis was verified in this study.

Methods

We examined 24 patients with severe sepsis; the patients were subdivided by outcome into early death (n = 5), mid-term survival (survival through severe sepsis but death within six months or continued hospitalization for six months, n = 6), and long-term survival (recovery and survival for more than six months, n = 13) groups. The levels of CD3⁺, CD4⁺, CD8⁺, and CD19⁺ lymphocytes were analyzed by flow cytometry, and the plasma levels of carbonic anhydrase IX (CA IX), MCP-1, IL-6, IL-7, IL-8, and IL-10 were measured by ELISA on days 0, 1, 2, and 3. A statistical comparison of the variables in the groups was conducted using a mixed model.

Results

The plasma levels of MCP-1, IL-6, and IL-8 in early death and survivors were significantly different, and all had p values <0.01. The plasma levels of MCP-1, IL-6, and IL-8 were also significantly different in mid-term survivors and long-term survivors, with p values of <0.01, 0.04, and <0.01, respectively.

Conclusions

Our data support the hypothesis that survivors have a weaker pro-inflammatory response than non-survivors, but the mid-term survivors did not have a more pronounced anti-inflammatory response. The levels of pro-inflammatory cytokines in the mid-term and long-term survivors were significantly different.

【 授权许可】

   
2014 Hong et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Suffredini AF, Munford RS: Novel therapies for septic shock over the past 4 decades. JAMA 2011, 306:194-199.
• [2]Angus DC: The search for effective therapy for sepsis back to the drawing board? JAMA 2011, 306:2614-2615.
• [3]Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348:1546-1554.
• [4]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, 29:1303-1310.
• [5]Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D, Sepsis Occurrence in Acutely III Patients Investigators: Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006, 34:344-353.
• [6]Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 2003, 348:138-150.
• [7]Ward NS, Casserly B, Ayala A: The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med 2008, 29:617-625.
• [8]Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE: Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med 1997, 25:1298-1307.
• [9]Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T: Fox3+CD25+CD4+ natural T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006, 212:8-27.
• [10]Blumenstein M, Boekstegers P, Fraunberger P, Andreesen R, Xiegler-Heitbrock HW, Fingerle-Rowson G: Cytokine production precedes the expansion of CD14+CD16+ monocytes in human sepsis: a case report of a patient with self-induced septicemia. Shock 1997, 8:73-75.
• [11]Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT: Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007, 11:R49. BioMed Central Full Text
• [12]Eckert AW, Kappler M, Schubert J, Taubert H: Correlation of expression of hypoxia-related proteins with prognosis in oral squamous cell carcinoma patients. Oral Maxillofac Surg 2012, 16:189-196.
• [13]Wolfinger R, Chang M: Comparing the SAS GLM and MIXED Procedures for Repeated Measures. In In Proceedings of the Twentieth Annual SAS Users Group Conference. Cary, NC: SAS Institute Inc; 1995.
• [14]Shubin NJ, Monaghan SF, Ayala A: Anti-inflammatory mechanisms of sepsis. Contrib Microbiol 2011, 17:108-124.
• [15]Aziz M, Jacob A, Yang WL, Matsuda A, Wang P: Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol 2013, 93:329-342.
• [16]Hoser GA, Skirecki T, Zlotorowicz M, Zielińska-Borkowska U, Kawiak J: Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study. Folia Histochem Cytobiol 2012, 50:420-426.
• [17]Chen X, Ye J, Ye J: Analysis of peripheral blood lymphocyte subsets and prognosis in patients with septic shock. Microbiol Immunol 2011, 55:736-742.