Soluble ST2 Plasma Concentrations Predict Mortality in Severe Sepsis

Overview

Journal Intensive Care Med

Specialty Critical Care

Date 2010 Feb 13

PMID 20151106

Citations 63

Authors

Jacobien J Hoogerwerf

Michael W T Tanck

Marieke A D van Zoelen

Xavier Wittebole

Pierre-Francois Laterre

Tom van der Poll

Affiliations

Soon will be listed here.

Abstract

Purpose: Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors, including membrane-bound ST2. We investigated the release of soluble ST2 (sST2), a decoy receptor that inhibits membrane-bound ST2 signaling, during sepsis.

Methods: The study population comprised 95 patients with severe sepsis admitted to one of two intensive care units (ICUs) at the day the diagnosis of severe sepsis was made. Blood was obtained daily from admission (day 0) until day 7 and finally at day 14. Twenty-four healthy subjects served as controls. sST2 and cytokines were measured in serum.

Results: Mortality among patients was 34% in the ICU and 45% in the hospital. On admission, sepsis patients had higher sST2 levels [10,989 (7,871-15,342) pg/ml, geometric mean (95% confidence interval, CI)] than controls [55 (20-145) pg/ml, P < 0.0001]. Serum sST2 remained elevated in patients from day 0 to 14 and correlated with disease severity scores (P < 0.001) and cytokine levels on day 0 and during course of disease (P < 0.0001). Nonsurvivors displayed elevated sST2 levels compared with survivors of the intensive care unit (P < 0.0001).

Conclusions: Sepsis results in sustained elevation of serum sST2 levels, which correlates with disease severity and mortality.

Citing Articles

Interleukin-33: A Double-Edged Sword in Sepsis.

Liu S, Yue Y, Wu Q, Zhang L Transl Perioper Pain Med. 2025; 11(2):612-619.

PMID: 39991638 PMC: 11845250. DOI: 10.31480/2330-4871/188.

The diagnostic and prognostic value of soluble ST2 in Sepsis.

Ye X, Wang J, Hu L, Zhang Y, Li Y, Xuan J Front Med (Lausanne). 2024; 11:1487443.

PMID: 39640977 PMC: 11617550. DOI: 10.3389/fmed.2024.1487443.

ST2 and Reg3α: Can they predict aGvHD, steroid refractoriness and transplant-related mortality in pediatric patients after HSCT?.

Ozturk G, Bayrakoglu D, Haskologlu S, Baskin K, Deveci N, Ince E Hematol Transfus Cell Ther. 2024; 46 Suppl 6:S129-S135.

PMID: 38658297 PMC: 11726067. DOI: 10.1016/j.htct.2024.02.026.

Serum interleukin-33 and soluble suppression of tumorigenicity 2 in pediatric leukemia with febrile neutropenia.

Polat M, Sonmez C, Yarali N, Ozbek N Eur J Pediatr. 2024; 183(5):2155-2162.

PMID: 38367066 DOI: 10.1007/s00431-024-05478-7.

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy.

Wang L, Dai W, Zhu R, Long T, Zhang Z, Song Z Front Med (Lausanne). 2024; 10:1278879.

PMID: 38259843 PMC: 10801257. DOI: 10.3389/fmed.2023.1278879.

References

Becerra A, Warke R, de Bosch N, Rothman A, Bosch I . Elevated levels of soluble ST2 protein in dengue virus infected patients. Cytokine. 2008; 41(2):114-20. PMC: 2276732. DOI: 10.1016/j.cyto.2007.11.001. View

Marks J, Marks C, Luce J, Montgomery A, Turner J, Metz C . Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration. Am Rev Respir Dis. 1990; 141(1):94-7. DOI: 10.1164/ajrccm/141.1.94. View

Hayakawa H, Hayakawa M, Kume A, Tominaga S . Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem. 2007; 282(36):26369-80. DOI: 10.1074/jbc.M704916200. View

Angus D, Wax R . Epidemiology of sepsis: an update. Crit Care Med. 2001; 29(7 Suppl):S109-16. DOI: 10.1097/00003246-200107001-00035. View

Brint E, Xu D, Liu H, Dunne A, McKenzie A, ONeill L . ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol. 2004; 5(4):373-9. DOI: 10.1038/ni1050. View

Dellinger R, Carlet J, Gerlach H, Ramsey G, Levy M . The surviving sepsis guidelines: not another "groundhog day". Crit Care Med. 2004; 32(7):1601-2. DOI: 10.1097/01.ccm.0000130996.14896.f6. View

van der Poll T, Opal S . Host-pathogen interactions in sepsis. Lancet Infect Dis. 2007; 8(1):32-43. DOI: 10.1016/S1473-3099(07)70265-7. View

Hack C, Aarden L, Thijs L . Role of cytokines in sepsis. Adv Immunol. 1997; 66:101-95. DOI: 10.1016/s0065-2776(08)60597-0. View

Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y . Expression and function of the ST2 gene in a murine model of allergic airway inflammation. Clin Exp Allergy. 2002; 32(10):1520-6. DOI: 10.1046/j.1365-2745.2002.01494.x. View

10.

Kuroiwa K, Arai T, Okazaki H, Minota S, Tominaga S . Identification of human ST2 protein in the sera of patients with autoimmune diseases. Biochem Biophys Res Commun. 2001; 284(5):1104-8. DOI: 10.1006/bbrc.2001.5090. View

11.

Pinsky M, Vincent J, Deviere J, Alegre M, KAHN R, Dupont E . Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest. 1993; 103(2):565-75. DOI: 10.1378/chest.103.2.565. View

12.

Weinberg E, Shimpo M, Hurwitz S, Tominaga S, Rouleau J, Lee R . Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation. 2003; 107(5):721-6. DOI: 10.1161/01.cir.0000047274.66749.fe. View

13.

Oshikawa K, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Ohno S . Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med. 2001; 164(2):277-81. DOI: 10.1164/ajrccm.164.2.2008120. View

14.

Levy M, Fink M, Marshall J, Abraham E, Angus D, Cook D . 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003; 31(4):1250-6. DOI: 10.1097/01.CCM.0000050454.01978.3B. View

15.

Hotchkiss R, Karl I . The pathophysiology and treatment of sepsis. N Engl J Med. 2003; 348(2):138-50. DOI: 10.1056/NEJMra021333. View

16.

Shimpo M, Morrow D, Weinberg E, Sabatine M, Murphy S, Antman E . Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation. 2004; 109(18):2186-90. DOI: 10.1161/01.CIR.0000127958.21003.5A. View

17.

Calandra T, Gerain J, Heumann D, Baumgartner J, Glauser M . High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group. Am J Med. 1991; 91(1):23-9. DOI: 10.1016/0002-9343(91)90069-a. View

18.

Brunner M, Krenn C, Roth G, Moser B, Dworschak M, Jensen-Jarolim E . Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med. 2004; 30(7):1468-73. DOI: 10.1007/s00134-004-2184-x. View

19.

Sanada S, Hakuno D, Higgins L, Schreiter E, McKenzie A, Lee R . IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007; 117(6):1538-49. PMC: 1865027. DOI: 10.1172/JCI30634. View

20.

Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y . ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation. Biochem Biophys Res Commun. 2002; 299(1):18-24. DOI: 10.1016/s0006-291x(02)02578-0. View