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Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma

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Abstract

Objective

T1/ST2, a member of the interleukin (IL)-1 receptor superfamily, is predominantly expressed on type-2 T helper (Th2) cells but not Th1 cells, and plays a role in cell proliferation and Th2 immune response. The relation of soluble ST2, Th1-Th2 cytokine profile, and immunoglobulin (Ig) production in sepsis and trauma patients is not well known.

Design and setting

Case-control study at a university hospital intensive care unit.

Patients

Fifteen patients recruited within 24–48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h after admission to the ICU, 11 patients who underwent abdominal surgery, and 15 healthy volunteers served as control.

Measurements and results

ELISA was utilized to detect serum soluble ST2, IL-2, IFN-γ, IL-10, and Ig production. Serum levels of soluble ST2 were significantly increased in septic patients (8420±2169 pg/ml) as compared with trauma (2936±826 pg/ml), abdominal surgery (1423±373 pg/ml), and healthy controls (316±72 pg/ml; p<0.001, respectively). These results were accompanied by an increase of IgG1 and IgG2 production, and decrease of IL-2 and IFN-γ synthesis in septic patients. IL-10 was significantly increased in both septic and trauma patients.

Conclusions

Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.

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References

  1. Stone R (1994) Search for sepsis drugs goes on despite past failures. Science 264:365–367

    CAS  PubMed  Google Scholar 

  2. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE (1999) Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 27:1230–1251

    CAS  PubMed  Google Scholar 

  3. Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146

    CAS  PubMed  Google Scholar 

  4. Ferguson NR, Galley HF, Webster NR (1999) T helper subset ratios in patients with severe sepsis. Intensive Care Med 25:106–109

    Article  CAS  PubMed  Google Scholar 

  5. Roth G, Moser B, Krenn C, Brunner M, Haisjackl M, Gerlitz S, Wolner E, Boltz-Nitulescu G, Ankersmit HJ (2003) Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance. Biochem Biophys Res Commun 308:840–846

    Article  CAS  PubMed  Google Scholar 

  6. Tominaga S (1989) A putative protein of a growth specific cDNA from BALB/c–3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett 258:301–304

    Article  CAS  PubMed  Google Scholar 

  7. Yanagisawa K, Tagaki T, Tsukamoto T, Testuka T, Tominaga S (1993) Presence of a novel primary response gene ST2L, encoding a product highly similar to interleukin 1 receptor type 1. FEBS Lett 318:83–87

    Article  CAS  PubMed  Google Scholar 

  8. Tominaga, S, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Komatsu N (1999) Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM. Biochem Biophys Res Commun 264:14–18

    Article  CAS  PubMed  Google Scholar 

  9. Werenskiold AK, Hofmann S, Klemetz R (1989) Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts. Mol Cell Biol 9:5207–5214

    CAS  PubMed  Google Scholar 

  10. Tominaga SI, Inazawa J, Tsuji S (1996) Assignment of human ST2 gene to chromosome 2 at q11.2. Hum Genet 97:561–563

    Article  CAS  PubMed  Google Scholar 

  11. Moritz DR, Gheyselinck J, Klemenz R (1998) Expression analysis of the soluble and membrane-associated forms of the interleukin-1 receptor-related T1 protein in primary mast cells and fibroblasts. Hybridoma 17:107–116

    CAS  PubMed  Google Scholar 

  12. Bergers G, Reikerstorfer A, Braselmann S, Graninger P, Busslinger M (1994) Alternative promotor usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. EMBO J 13:1176–1188

    CAS  PubMed  Google Scholar 

  13. Dale M, Nicklin MJ (1999) Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 57:177–179

    Article  CAS  PubMed  Google Scholar 

  14. Yanagisawa K, Naito Y, Kuroiwa K, Arai T, Furukawa Y, Tomizuka H, Miura Y, Kasahara T, Tetsuka T, Tominaga S (1997) The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. J Biochem (Tokyo) 121:95–103

    Google Scholar 

  15. Xu D, Chan WL, Leung PB, Huang F, Wheeler R, Piedrafita, Robinson JH, Liew FY (1998) Selective expression of stable surface molecule on type 2 but not type 1 helper T cells. J Exp Med 187:787–794

    Article  CAS  PubMed  Google Scholar 

  16. Lohning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos JC, Levinson D, Radbruch A, Kamradt T (1998) T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5 and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA 95:6930–6935

    Article  CAS  PubMed  Google Scholar 

  17. Moritz DR, Rodewald HR, Gheyselinck J, Klemenz R (1998) The IL-1 receptor-related T1 antigen is expressed on immature and mature mast cells and on fetal blood mast cell progenitors. J Immunol 161:4866–4874

    CAS  PubMed  Google Scholar 

  18. Oshikawa K, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Ohno S, Tominaga SI, Sugiyama Y (2001) Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med 164:277–281

    CAS  PubMed  Google Scholar 

  19. Oshikawa K, Yanagisawa K, Tominaga SI, Sugiyama Y (2002) Expression and function of the ST2 gene in a murine model of allergic airway inflammation. Clin Exp Allergy 32:1520–1526

    Article  CAS  PubMed  Google Scholar 

  20. Tajima S, Oshikawa K, Tominaga SI, Sugiyama Y (2002) The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis. Chest 124:1206–1214

    Article  Google Scholar 

  21. Kuroiwa K, Arai T, Okazaki M, Minota S, Tominaga S (2001) Identification of human ST2 protein in the sera of patients with autoimmune diseases. Biochem Biophys Res Commun 284:1104–1108

    Article  CAS  PubMed  Google Scholar 

  22. Cameron SB, Nawijn MC, Kum WW, Savelkoul HF, Chow AW (2001) Regulation of helper T cell responses to staphylococcal superantigens. Eur Cytokine Netw 12:210–222

    CAS  PubMed  Google Scholar 

  23. Spolarics Z, Siddiqi M, Siegel JH, Garcia ZC, Stein DS, Denny T, Deitch EA (2003) Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients. Crit Care Med 31:1722–1729

    Article  CAS  PubMed  Google Scholar 

  24. Sweet MJ, Leung BP, Kang D, Sogaard M, Schultz K, Trajkovic V, Campbell CC, Xu D, Liew FY (2001) A novel pathway regulating lipopolysaccharide-induced shock by ST2T1 via inhibition of Toll-like receptor 4 expression. J Immunol 166:6633–6639

    CAS  PubMed  Google Scholar 

  25. Weinberg EO, Shimpo M, Hurwitz S, Tominaga SI, Rouleau JL, Lee RT (2003) Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 107:721–726

    Article  PubMed  Google Scholar 

  26. Gachter T, Moritz DR, Gheyselinck J, Klemenz R (1998) GATA-dependent expression of the interleukin-1 receptor-related T1 gene in mast cells. Mol Cell Biol 18:5320–5331

    CAS  PubMed  Google Scholar 

  27. Brint EK, Fitzgerald KA, Smith P, Coyle AJ, Gutierrez-Ramos JC, Fallon PG, O’Neill LAJ (2002) Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. J Biol Chem 277:49205–49211

    Article  CAS  PubMed  Google Scholar 

  28. Kumar S, Minnich MD, Young PR (1995) ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1. J Biol Chem 270:27905–27913

    Article  CAS  PubMed  Google Scholar 

  29. Meisel C, Bonhagen K, Lohning M, Coyle AJ, Gutierrez-Ramos JC, Radbruch A, Kamradt T (2001) Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking. J Immunol 166:3143–3150

    CAS  PubMed  Google Scholar 

  30. Kropf P, Bickle Q, Herath S, Klemenz R, Muller I (2002) Organ-specific distribution of CD4+T1/ST2+ Th2 cells in Leishmania major infection. Eur J Immunol 32:2450–2459

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This paper was supported by grant 9449, Austrian National Bank. H.J. Ankersmit designed the study.

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Authors and Affiliations

  1. Department of Surgery, University of Vienna, AKH, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Markus Brunner, Georg Roth, Andreas Spittler, Thomas Sautner, Ernst Wolner & Hendrik Jan Ankersmit

  2. Department of Anaesthesiology, University of Vienna, Vienna, Austria

    Claus Krenn & Martin Dworschak

  3. Department of Surgery, Columbia University, New York, New York, USA

    Bernhard Moser

  4. Department of Pathophysiology, University of Vienna, Vienna, Austria

    Erika Jensen-Jarolim & George Boltz-Nitulescu

  5. Department of Cardiac Surgery, University of Innsbruck, Innsbruck, Austria

    Nico Bonaros

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  1. Markus Brunner
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  2. Claus Krenn
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  3. Georg Roth
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  12. Hendrik Jan Ankersmit
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Correspondence to Hendrik Jan Ankersmit.

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Brunner, M., Krenn, C., Roth, G. et al. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med 30, 1468–1473 (2004). https://doi.org/10.1007/s00134-004-2184-x

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  • DOI: https://doi.org/10.1007/s00134-004-2184-x

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