Increased IL-17 and TGF-ß serum levels in peripheral blood of patients with ß-thalassemia major: implication for continual transfusions role in T helper 17-mediated proinflammatory responses

Increased IL-17 and TGF-ß serum levels in peripheral blood of patients with ß-thalassemia major: implication for continual transfusions role in T helper 17-mediated proinflammatory responses

Background/aim: Recent studies have shown that IL-17-producing CD4+ T helper (Th17) cells play an important role in proinflammatory processes. In this report we analyzed IL-17, IL-21, and TGF-β serum levels in the peripheral blood of Iranian beta-thalassemia major patients that clinically exhibited splenectomy and iron overload. Materials and methods: Blood samples were collected from 43 beta-thalassemia patients and 43 healthy individuals with no history of malignancies or autoimmune disorders. Then serum levels of IL-17, IL-21, and TGF-β were measured by enzyme linked immunosorbent assay (ELISA). Results: The levels of IL-17 (P = 0.005) and TGF-β (P < 0.001) were significantly higher in the thalassemia patients compared to the healthy control. No significant differences in the level of serum IL-21 was observed between the patients and controls. There were no significant differences in serum levels of IL-17, IL-21, and TGF-β between patients with high or low serum levels of ferritin. Conclusion: Multiple blood transfusions cause constant immune stimulation, as a result of repeated exposure to new alloantigens. This might have significant effects on the stimulation of cytokine producing cells in those patients and cytokine profile can be used as a related marker for assessing disease severity and consequently therapeutic intervention.

___

  • 1. Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med 2005; 353: 1135-1146.
  • 2. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997; 89: 739-761.
  • 3. Weiss G. Iron and immunity: a double-edged sword. Eur J Clin Invest 2002; 32 Suppl 1: 70-78.
  • 4. Cunningham-Rundles S, Giardina PJ, Grady RW, Califano C, McKenzie P, De Sousa M. Effect of transfusional iron overload on immune response. J Infect Dis 2000; 182 Suppl 1: S115-S121.
  • 5. Farmakis D, Giakoumis A, Polymeropoulos E, Aessopos A. Pathogenetic aspects of immune deficiency associated with beta-thalassemia. Med Sci Monit 2003; 9: RA19-22.
  • 6. Bozdogan G, Erdem E, Demirel GY, Yildirmak Y. The role of Treg cells and FoxP3 expression in immunity of β-thalassemia major and β-thalassemia trait patients. Pediatr Hematol Oncol 2010; 27: 534-545.
  • 7. Kadymova EA. The features of immune status of major betathalassemia patients during various periods after splenectomy. Georgian Med News 2009: 39-44 (in Russian).
  • 8. Bao W, Zhong H, Li X, Lee MT, Schwartz J, Sheth S, Yazdanbakhsh K. Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and beta-thalassemia major. Am J Hematol 2011; 86: 1001-1006.
  • 9. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348-2357.
  • 10. Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol 2002; 2: 933-944.
  • 11. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6: 1123-1132.
  • 12. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005; 6: 1133-1141.
  • 13. Xu S, Cao X. Interleukin-17 and its expanding biological functions. Cell Mol Immunol 2010; 7: 164-174.
  • 14. Louten J, Boniface K, de Waal Malefyt R. Development and function of TH17 cells in health and disease. J Allergy Clin Immunol 2009; 123: 1004-1011.
  • 15. Peck A, Mellins ED. Breaking old paradigms: Th17 cells in autoimmune arthritis. Clin Immunol 2009; 132: 295-304.
  • 16. Sallusto F, Lanzavecchia A. Human Th17 cells in infection and autoimmunity. Microbes Infect 2009; 11: 620-624.
  • 17. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA, Laurence A, Michalowska A, Mamura M, Lonning S et al. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 2008; 68: 3915-3923.
  • 18. Passos ST, Silver JS, O’Hara AC, Sehy D, Stumhofer JS, Hunter CA. IL-6 promotes NK cell production of IL-17 during toxoplasmosis. J Immunol 2010; 184: 1776-1783.
  • 19. Mucida D, Cheroutre H. TGFbeta and retinoic acid intersect in immune-regulation. Cell Adh Migr 2007; 1: 142-144.
  • 20. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007; 317: 256-260.
  • 21. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 2010; 10: 479-489.
  • 22. Khatami M. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases. Cell Biochem Biophys 2009; 55: 55- 79.
  • 23. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23- IL-17 immune pathway. Trends Immunol 2006; 27: 17-23.
  • 24. Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets 2012.
  • 25. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 2008; 454: 350-352.
  • 26. Gharagozloo M, Karimi M, Amirghofran Z. Double-faced cell-mediated immunity in beta-thalassemia major: stimulated phenotype versus suppressed activity. Ann Hematol 2009; 88: 21-27.
  • 27. Ozturk O, Yaylim I, Aydin M, Yilmaz H, Agachan B, Demiralp E, Isbir T. Increased plasma levels of interleukin-6 and interleukin-8 in beta-thalassaemia major. Haematologia (Budap) 2001; 31: 237-244.
  • 28. Gangemi S, Merendino RA, Meo A, Minciullo PL, Briuglia S, Merlino MV, Rigoli L, Tomasello C, Salpietro CD. Serum levels of interleukin-18 in splenectomized and nonsplenectomized thalassemic patients: preliminary considerations. Acta Haematol 2003; 110: 45-47.
  • 29. Wanachiwanawin W, Wiener E, Siripanyaphinyo U, Chinprasertsuk S, Mawas F, Fucharoen S, Wickramasinghe SN, Pootrakul P, Visudhiphan S. Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta(o)- thalassemia/HbE and their clinical significance. J Interferon Cytokine Res 1999; 19: 105-111.
  • 30. Butthep P, Rummavas S, Wisedpanichkij R, Jindadamrongwech S, Fucharoen S, Bunyaratvej A. Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia. Am J Hematol 2002; 70: 100- 106.
  • 31. Balouchi S, Gharagozloo M, Esmaeil N, Mirmoghtadaei M, Moayedi B. Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy. Immunopharmacology and immunotoxicology 2014; 1-4.
  • 32. Salsaa B, Zoumbos N. A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with β‐thalassaemia. Clinical & Experimental Immunology 1997; 107: 589-592.
  • 33. Mencacci A, Cenci E, Boelaert JR, Bucci P, Mosci P, d’Ostiani CF, Bistoni F, Romani L. Iron overload alters innate and T helper cell responses to Candida albicans in mice. Journal of Infectious Diseases 1997; 175: 1467.
  • 34. Omara FO, Blakley BR. The effects of iron deficiency and iron overload on cell-mediated immunity in the mouse. British Journal of Nutrition. 1994; 72: 899-909.
  • 35. Moshtaghi-Kashanian GR, Gholamhoseinian A, Hoseinimoghadam A, Rajabalian S. Splenectomy changes the pattern of cytokine production in beta-thalassemic patients. Cytokine 2006; 35: 253-257.
  • 36. Lombardi G, Matera R, Minervini MM, Cascavilla N, D’Arcangelo P, Carotenuto M, Di Giorgio G, Musto P. Serum levels of cytokines and soluble antigens in polytransfused patients with beta-thalassemia major: relationship to immune status. Haematologica 1994; 79: 406-412.
  • 37. Appay V, Rowland-Jones SL. Premature ageing of the immune system: the cause of AIDS? Trends in Immunology 2002; 23: 580-585.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Saliha EKŞİ, Nebahat EJDER, Fatih YILMAZ, Ayşe ERTÜRK, Cemal SANDALLI

First report on the distribution of 3435C>T ABCB1/MDR1polymorphism in healthy Bosniak population

Grazyna ADLER, Anna PAWINSKA-MATECKA, AGNIESZKA GARSTKA, Nermin Nusret SALKIC, AMINA VALJEVAC, Beata KARAKIEWICZ

Impact of different anesthetic managements in outcomes of transcatheteraortic valve implantation: the first Turkish experience

Ezgi ERKILIÇ, Elvin KESİMCİ*, Orhan KANBAK, Tülin GÜMÜŞ

Levent VAHDETTIN, Seçil AKSOY, Ulaş ÖZ, Kaan ORHAN

Evaluation of the gastrointestinal findings of nodulocystic acnepatients during systemic isotretinoin therapy

Seçil ÖZKAN, Duru TABANLIOĞLU ONAN, Ufuk SAMSAR, Refika Ferda ARTÜZ, Nuran ALLI, Burcu HAZAR TANTOĞLU, Hasan Tankut KÖSEOĞLU

Effectiveness of P6 acupoint electrical stimulation in preventing postoperativenausea and vomiting following laparoscopic surgery

Aik Hoe YEOH, Shereen Suet Ping TANG2, Norsidah ABDUL MANAP, Wan Rahiza WAN MAT, Muhamad Rahimi CHE HASSAN, Shuraya SAID, Raha ABDUL RAHMAN

The utility of the TIMI risk index on admission for predicting angiographic no-reflow after primary percutaneous coronary intervention in patients with STEMI

Mehmet Ata AKIL, Mehmet Zihni BİLİK, Nizamettin TOPRAK, Nihat POLAT, Halit ACET, Mehmet ÖZBEK, Necdet ÖZAYDOĞDU, Leyla ÇİFTÇİ, Murat YÜKSEL, Sait ALAN, Abdulkadir YILDIZ, Faruk ERTAŞ, Mesut AYDIN

Grazyna ADLER, Anna PAWINSKA-MATECKA, AGNIESZKA GARSTKA, Nermin Nusret SALKIC, AMINA VALJEVAC, Beata KARAKIEWICZ

Evaluation of the relationship between migraine disorder andoral comorbidities: multicenter randomized clinical trial

Cem PEŞKERSOY, Ayşegül KAYA, Şule PEKER, Necmi GÖKAY, Aycan ÜNALP

Brachiobasilic arteriovenous fistula with transpositionof the basilic vein: a multicenter study

Stelian PANTEA, Iustinian Michael BENGULESCU, Gabriela OROSAN, Irina STRAMBU, Victor Dan Eugen STRAMBU