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Profile of Th17 cytokines (IL-17, TGF-β, IL-6) and Th1 cytokine (IFN-γ) in patients with immune thrombocytopenic purpura

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Abstract

The data on polarization of the immune system towards T helper 1 (Th1) or T helper 2 (Th2) cells in immune thrombocytopenic purpura (ITP) are limited and contradictory. Th17 characterized by the production of Interleukin 17 (IL-17) has been shown to play a crucial part in the induction of autoimmune diseases. To further investigate the role of Th cytokines in the pathogenesis of ITP, we measured the plasma concentration of three Th17-associated cytokines [IL-17, transforming growth factor-ß (TGF-ß), IL-6] and Th1 cytokine interferon-γ (IFN-γ) in ITP patients, and evaluated their clinical relevance. The concentration of IL-17, TGF-ß, IL-6, and IFN-γ in plasma specimens from 29 adults with chronic ITP and 38 controls was analyzed by enzyme-linked immunosorbent assay method. No significant differences of Th17 cytokines (IL-17, TGF-ß, and IL-6) and Th1 cytokine (IFN-γ) concentration were observed between patients with active ITP and the control group. And the IFN-γ/IL-17 ratio representing Th1/Th17 cytokine profile was not significantly different between ITP patients and control, either. However, significantly positive correlation between IL-6 and IFN-γ in ITP patients was observed (r = 0.48, P = 0.01). Among the ITP patients, Plasma IL-17 levels in male were marginally higher than those in female, while similar for TGF-ß, IL-6 or IFN-γ. There was a significantly positive correlation between age and IL-6 concentration in ITP patients (r = 0.56, P = 0.0002), while no statistical significance between age and the other three cytokines. No significant correlation between cytokine concentrations and platelets or megakaryocytes number was found in ITP patients. In summary, ITP may not be associated with changes of plasma Th17 and Th1 cytokine concentrations relative to control population.

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References

  1. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914 doi:10.1074/jbc.M207577200

    Article  PubMed  CAS  Google Scholar 

  2. Andersson PO, Stockelberg D, Jacobsson S, Wadenvik H (2000) A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura. Ann Hematol 79:507–513 doi:10.1007/s002770000177

    Article  PubMed  CAS  Google Scholar 

  3. Butrimiene I, Jarmalaite S, Ranceva J, Venalis A, Jasiuleviciute L, Zvirbliene A (2004) Different cytokine profiles in patients with chronic and acute reactive arthritis. Rheumatology (Oxford) 43:1300–1304 doi:10.1093/rheumatology/keh323

    Article  CAS  Google Scholar 

  4. Cines DB, Blanchette VS (2002) Immune thrombocytopenic purpura. N Engl J Med 346:995–1008 doi:10.1056/NEJMra010501

    Article  PubMed  Google Scholar 

  5. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B et al (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748 doi:10.1038/nature01355

    Article  PubMed  CAS  Google Scholar 

  6. Elson CO, Cong Y, Brandwein S, Weaver CT, McCabe RP, Mähler M et al (1998) Experimental models to study molecular mechanisms underlying intestinal inflammation. Ann N.Y. Acad Sci 859:85–95 doi:10.1111/j.1749-6632.1998.tb11113.x

    Article  PubMed  CAS  Google Scholar 

  7. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ et al (1996) Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 88:3–40

    PubMed  CAS  Google Scholar 

  8. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM et al (2005) Interleukin 17-producing CD4(+) effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132 doi:10.1038/ni1254

    Article  PubMed  CAS  Google Scholar 

  9. Hoffman R, Zaknoen S, Yang HH, Bruno E, LoBuglio AF, Arrowsmith JB et al (1985) An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura. N Engl J Med 312:1170–1174

    PubMed  CAS  Google Scholar 

  10. Karlsson FA, Berne C, Björk E, Kullin M, Li Z, Ma JY et al (2000) Beta-cell activity and destruction in type 1 diabetes. Ups J Med Sci 105:85–95

    PubMed  CAS  Google Scholar 

  11. Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S (2007) T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med 204:41–47 doi:10.1084/jem.20062259

    Article  PubMed  CAS  Google Scholar 

  12. Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476 doi:10.1016/j.immuni.2004.08.018

    Article  PubMed  CAS  Google Scholar 

  13. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD et al (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240 doi:10.1084/jem.20041257

    Article  PubMed  CAS  Google Scholar 

  14. McMillan R, Luiken GA, Levy R, Yelenosky R, Longmire RL (1978) Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA 239:2460–2462 doi:10.1001/jama.239.23.2460

    Article  PubMed  CAS  Google Scholar 

  15. Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146 doi:10.1016/0167-5699(96)80606-2

    Article  PubMed  CAS  Google Scholar 

  16. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA et al (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198:1951–1957 doi:10.1084/jem.20030896

    Article  PubMed  CAS  Google Scholar 

  17. Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I et al (2002) Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17:375–387 doi:10.1016/S1074-7613(02)00391-6

    Article  PubMed  CAS  Google Scholar 

  18. Nomura S, Yanabu M, Kido H, Lan XG, Ichiyoshi H, Katsura K et al (1995) Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura. Eur J Haematol 55:49–56

    Article  PubMed  CAS  Google Scholar 

  19. Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H et al (2003) High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol 71:283–288 doi:10.1034/j.1600-0609.2003.00138.x

    Article  PubMed  CAS  Google Scholar 

  20. Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC et al (2004) Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood 103:2645–2647 doi:10.1182/blood-2003-07-2268

    Article  PubMed  CAS  Google Scholar 

  21. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH et al (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133–1141 doi:10.1038/ni1261

    Article  PubMed  CAS  Google Scholar 

  22. Stahl CP, Zucker-Franklin D, McDonald TP (1986) Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP. Blood 67:421–428

    PubMed  CAS  Google Scholar 

  23. Stasi R, Del Poeta G, Stipa E, Evangelista ML, Trawinska MM, Cooper N et al (2007) Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 110:2924–2930 doi:10.1182/blood-2007-02-068999

    Article  PubMed  CAS  Google Scholar 

  24. Vainchenker W, Deschamps JF, Bastin JM, Guichard J, Titeux M, Breton-Gorius J et al (1982) Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in vivo cells from normal and leukemia patients. Blood 59:514–521

    PubMed  CAS  Google Scholar 

  25. Wang HL (2003) Clinical hematologic analysis. In: Cheng WB, Wang YC (eds) Diagnostics, 5th Ed. The People’s Health, Peking, pp 301–302 (In Chinese)

    Google Scholar 

  26. Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R et al (2005) Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 90:914–923

    PubMed  CAS  Google Scholar 

  27. Webber NP, Mascarenhas JO, Crow MK, Bussel J, Schattner EJ (2001) Functional properties of lymphocytes in idiopathic thrombocytopenic purpura. Hum Immunol 62:1346–1355 doi:10.1016/S0198-8859(01)00348-2

    Article  PubMed  CAS  Google Scholar 

  28. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B et al (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116:1310–1316 doi:10.1172/JCI21404

    Article  PubMed  CAS  Google Scholar 

  29. Yoshimura C, Nomura S, Nagahama M, Ozaki Y, Kagawa H, Fukuhara S (2000) Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura. Eur J Haematol 64:219–224 doi:10.1034/j.1600-0609.2000.9o096.x

    Article  PubMed  CAS  Google Scholar 

  30. Zhang L, Li H, Zhao H, Ji X, Yang R (2003) Hepatitis C virus-related adult chronic idiopathic thrombocytopenic purpura: experience from a single Chinese center. Eur J Haematol 70:196–197 doi:10.1034/j.1600-0609.2003.00032.x

    Article  PubMed  Google Scholar 

  31. Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56:2936–2946 doi:10.1002/art.22866

    Article  PubMed  CAS  Google Scholar 

  32. Zhou B, Zhao H, Yang RC, Han ZC (2005) Multi-dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol 54:107–116 doi:10.1016/j.critrevonc.2004.12.004

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. Fengqiang Wang and Cheng Liu for their reviewing and suggesting changes to the manuscript. This study was partially supported by grants from the National Natural Science Foundation (30600680, 30770922, 30470742, 30570779, 30600259, 30628015 and 30300312), 973 Project (2006CB503800), Key Clinical Research Project of Chinese Ministry of Health (2007–2009), Research Project of National Public Fare (200802031), and the Shandong Technological Development Project (2005BS03022).

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Authors and Affiliations

  1. Department of Hematology, Qilu Hospital, Shandong University, 107 WenhuaXi Road, Jinan, 250012, People’s Republic of China

    Daoxin Ma, Xiaojuan Zhu, Ping Zhao, Chunhong Zhao, Xiaofang Li, Yuanyuan Zhu, Lizhen Li, Jianzhi Sun, Jun Peng, Chunyan Ji & Ming Hou

  2. Department of Hematology, Jinan Central Hospital, Jinan, 250013, People’s Republic of China

    Ping Zhao

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  1. Daoxin Ma
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Ma, D., Zhu, X., Zhao, P. et al. Profile of Th17 cytokines (IL-17, TGF-β, IL-6) and Th1 cytokine (IFN-γ) in patients with immune thrombocytopenic purpura. Ann Hematol 87, 899–904 (2008). https://doi.org/10.1007/s00277-008-0535-3

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