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Post-Transplant Cytokines

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation

Bone Marrow Transplantation volume 33, pages 93–98 (2004)Cite this article

Summary:

The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T3 decreased to a nadir 3 weeks post-BMT and serum T4 was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-α increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T3 and T4 levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T4 at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-α were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

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References

  1. Hennemann G, Doctor R, Krenning EP . Causes and effects of the low T3 syndrome during caloric deprivation and non-thyroidal illness: an overview. Acta Med Aust 1988; 15: 42–45.

    Google Scholar 

  2. Cherem HJ, Nellen HH, Barabejski FG et al. Thyroid function and abdominal surgery. A longitudinal study. Arch Med Res 1992; 23: 143–147.

    Google Scholar 

  3. Chow CC, Mak TW, Chan CH et al. Euthyroid sick syndrome in tuberculosis before and after treatment. Ann Clin Biochem 1995; 32: 385–391.

    Article  PubMed  Google Scholar 

  4. Phillips RH, Valente WA, Caplan ES et al. Circulating thyroid hormone changes in acute trauma: prognostic implications for clinical outcome. J Trauma 1995; 24: 116–119.

    Article  Google Scholar 

  5. Vardarli I, Schmidt R, Wdowinski JM et al. The hypothalamo-hypophyseal thyroid axis, plasma protein concentrations and the hypophyseogonadal axis in low T3 syndrome following acute myocardial infarct. Klin Wochenschr 1987; 65: 129–133.

    Article  CAS  PubMed  Google Scholar 

  6. DeGroot LJ . Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab 1999; 84: 151–164.

    Article  CAS  Google Scholar 

  7. Maldonado LS, Murata GH, Hershman JM et al. Do thyroid function tests independently predict survival in the critically ill? Thyroid 1992; 2: 119–123.

    Article  CAS  PubMed  Google Scholar 

  8. Vaughan GM, Mason Jr AD, McManus WF et al . Alterations of mental status and thyroid hormones after thermal injury. J Clin Endocrinol Metab 1985; 60: 1221–1225.

    Article  CAS  PubMed  Google Scholar 

  9. De Marinis L, Mancini A, Masala R et al. Evaluation of pituitary–thyroid axis response to acute myocardial infarction. J Endocrinol Invest 1985; 8: 507–511.

    Article  CAS  PubMed  Google Scholar 

  10. Wartofsky L, Burman KD . Alterations in thyroid function in patients with systemic illness: the ‘euthyroid sick syndrome’. Endocr Rev 1982; 3: 164–217.

    Article  CAS  PubMed  Google Scholar 

  11. Vexiau P, Perez-Castiglioni P, Socie G et al. The ‘euthyroid sick syndrome’: incidence, risk factors and prognostic value soon after allogeneic bone marrow transplantation. Br J Hematol 1993; 85: 778–782.

    Article  CAS  Google Scholar 

  12. Schulte C, Reinhardt W, Beelen D et al. Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation. Bone Marrow Transplant 1998; 22: 1171–1178.

    Article  CAS  PubMed  Google Scholar 

  13. Reincke M, Allolio B, Petzke F et al. Thyroid dysfunction in African trypanosomiasis: a possible role for inflammatory cytokines. Clin Endocrinol (Oxf) 1993; 39: 455–461.

    Article  CAS  Google Scholar 

  14. Boelen A, Platvoet-Ter Schiphorst MC, Wiersinga WM . Association between serum interleukin-6 and serum 3,5,3′-triiodothyronine in nonthyroidal illness. J Clin Endocrinol Metab 1993; 77: 1695–1699.

    CAS  PubMed  Google Scholar 

  15. Bartalena L, Brogioni S, Grasso L et al. Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness. J Endocrinol Invest 1994; 17: 269–274.

    Article  CAS  PubMed  Google Scholar 

  16. Bartalena L, Brogioni S, Grasso L, Martino E . Interleukin-6 and the thyroid. Eur J Endocrinol 1995; 132: 386–393.

    Article  CAS  PubMed  Google Scholar 

  17. Mooradian AD, Reed RL, Osterweil D et al. Decreased serum triiodothyronine is associated with increased concentrations of tumor necrosis factor. J Clin Endocrinol Metab 1990; 71: 1239–1242.

    Article  CAS  PubMed  Google Scholar 

  18. Hashimoto H, Igarashi N, Yachic A et al. The relationship between serum levels of interleukin-6 and thyroid hormone in children with acute respiratory infection. J Clin Endocrinol Metab 1994; 78: 288–291.

    CAS  PubMed  Google Scholar 

  19. Amado JA, Lopez-Espadas F, Vazquez-Barquero A et al. Blood levels of cytokines in brain dead patients: relationship with circulating hormones and acute-phase reactants. Metabolism 1995; 44: 812–816.

    Article  CAS  PubMed  Google Scholar 

  20. Yokoc T, Iino Y, Takei H et al. Changes of cytokines and thyroid function in patients with recurrent breast cancer. Anticancer Res 1997; 17: 695–697.

    Google Scholar 

  21. Murai H, Murakami S, Ishida K et al. Elevated serum interleukin-6 and decreased thyroid hormone levels in post-operative patients and effects of IL-6 on thyroid cell function in vitro. Thyroid 1996; 6: 601–606.

    Article  CAS  PubMed  Google Scholar 

  22. Saatvedt K, Lindberg H . Depressed thyroid function following pediatric cardiopulmonary bypass: association with interleukin-6 release? Scand J Thorac Cardiovasc Surg 1996; 30: 61–64.

    Article  CAS  PubMed  Google Scholar 

  23. Davies PH, Black EG, Sheppard MC et al. Relationship between serum interleukin-6 and thyroid hormone concentrations in 270 hospital in-patients with non-thyroidal illness. Clin Endocrinol (Oxf) 1996; 44: 199–205.

    Article  CAS  Google Scholar 

  24. Hershman JM, Eriksen E, Kaufman N et al. Thyroid function tests in patients undergoing bone marrow transplantation. Bone Marrow Transplant 1990; 6: 49–51.

    CAS  PubMed  Google Scholar 

  25. Wehmann RE, Gregerman RI, Burns WH et al. Suppression of thyrotropin in the low-thyroxine state of severe nonthyroidal illness. N Engl J Med 1985; 312: 546–552.

    Article  CAS  PubMed  Google Scholar 

  26. Bartalena L, Bogazzi F, Brogioni S et al. Role of cytokines in the pathogenesis of the euthyroid sick syndrome. Eur J Endocrinol 1998; 138: 603–614.

    Article  CAS  PubMed  Google Scholar 

  27. Rowbottom AW, Riches PG, Downie C et al. Monitoring cytokine production in peripheral blood during acute graft-versus-host disease following allogeneic bone marrow transplantation. Bone Marrow Transplant 1993; 12: 635–641.

    CAS  PubMed  Google Scholar 

  28. Imamura M, Hashino S, Kobayashi S et al. Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels. Int J Hematol 1994; 60: 85–89.

    CAS  PubMed  Google Scholar 

  29. Remberger M, Ringden O, Markling L . TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant 1995; 15: 99–104.

    CAS  PubMed  Google Scholar 

  30. Sato K, Satoh T, Shizume K et al. Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-α, and interferon-γ in human thyrocytes in suspension culture. J Clin Endocrinol Metab 1990; 70: 1735–1743.

    Article  CAS  PubMed  Google Scholar 

  31. Tominaga T, Yamashita S, Nagayama Y et al. Interleukin-6 inhibits human thyroid peroxidase gene expression. Acta Endocrinol 1991; 124: 290–294.

    Article  CAS  Google Scholar 

  32. van der Poll T, Romijn JA, Wiersinga WM et al. Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J Clin Endocrinol Metab 1990; 71: 1567–1572.

    Article  CAS  PubMed  Google Scholar 

  33. Stouthard JM, van der Poll T, Endert E et al. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. J Clin Endocrinol Metab 1994; 79: 1342–1346.

    CAS  PubMed  Google Scholar 

  34. Boelen A, Platvoet-ter Schiphorst MC, Wiersinga WM . Immunoneutralization of interleukin-1, tumor necrosis factor, interleukin-6 or interferon does not prevent the LPS-induced sick euthyroid syndrome in mice. J Endocrinol 1997; 153: 115–122.

    Article  CAS  PubMed  Google Scholar 

  35. Nagaya T, Fujieda M, Otsuka G et al. A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome. J Clin Invest 2000; 106: 393–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Boelen A, Platvoet-ter Schiphorst MC, Wiersinga WM . Relationship between serum 3,5,3′-triiodothyronine and serum interleukin-8, interleukin-10 or interferon-γ in patients with nonthyroidal illness. J Endocrinol Invest 1996; 19: 480–483.

    Article  CAS  PubMed  Google Scholar 

  37. Kuku SF, Child DF, Nader S et al. Thyrotrophin and prolactin responsiveness to thyrotrophin releasing hormone in Cushing's disease. Clin Endocrinol (Oxf) 1975; 4: 437–442.

    Article  CAS  Google Scholar 

  38. Gamstedt A, Jarnerot G, Kagedal B et al. Corticosteroids and thyroid function. Different effects on plasma volume, thyroid hormones and thyroid hormone-binding proteins after oral and intravenous administration. Acta Med Scand 1979; 205: 379–383.

    Article  CAS  PubMed  Google Scholar 

  39. Uy HL, Reasner CA, Samuels MH . Pattern of recovery of the hypothalamic–pituitary–thyroid axis following radioactive iodine therapy in patients with Graves' disease. Am J Med 1995; 99: 173–179.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Cytokines determinations were made by Dr Hack-Joo Kim and Dr Young-Hoon Suh (Hyundai Research Institute, Hyundai Pharmaceutical Co., Incheon, Korea) and their help is gratefully acknowledged. This study was supported by the grant from the Korean Ministry of Health and Welfare (01-PJ1-PG1-01CH08-0001) and the Samsung Grant #SBRI C-A3-223-1.

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Authors and Affiliations

  1. Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    W Y Lee & S W Kim

  2. Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea

    M I Kang, K H Baek & K W Lee

  3. Miz Medi Hospital, Seoul, Korea

    K W Oh & E S Oh

  4. Hematopoietic Stem Cell Transplantation Center, The Catholic University of Korea, College of Medicine, Seoul, Korea

    D W Kim, W S Min & C C Kim

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  1. W Y Lee
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Correspondence to M I Kang.

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Lee, W., Kang, M., Oh, K. et al. Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation. Bone Marrow Transplant 33, 93–98 (2004). https://doi.org/10.1038/sj.bmt.1704304

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  • DOI: https://doi.org/10.1038/sj.bmt.1704304

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