Skip to main content
Log in

Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex vivo response to mitogen activation and cyclosporin A

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

To evaluate lymphocyte activation following mitogen and cyclosporin A (CsA) administration in peripheral blood of hyperthyroxinaemic and hypothyroid patients.

Materials and methods

Lymphocyte activation was evaluated by determining blastogenesis in 48 h cultured blood lymphocytes obtained from eight hyperthyroxinaemic and eight hypothyroid patients, following phytohaemagglutinin (PHA)-induced stimulation in the absence or presence of CsA. Twelve healthy volunteers served as controls.

Results and conclusions

Lymphocytes from hypothyroid patients exhibited reduced response to PHA and lower sensitivity to CsA compared with control, which could be attributed to their reduced activation capability coexisting with hypothyroidism. In hyperthyroxinaemic samples, the actions of high CsA concentrations were mostly targeted toward activated lymphoblasts. Considering the cellular targets that thyroid hormones and CsA may share, the therapeutic implications of their cross-talk need careful consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Foster MP, Montecino-Rodriguez E, Dorshkind K. Proliferation of bone marrow pro-B cells is dependent on stimulation by the pituitary/thyroid axis. J Immunol. 1999;163:5883–90.

    CAS  PubMed  Google Scholar 

  2. Arpin C, Pihlgren M, Fraichard A, Aubert D, Samarut J, Chassande O, et al. Effects of T3R alpha 1 and T3R alpha 2 gene deletion on T and B lymphocyte development. J Immunol. 2000;164:152–60.

    CAS  PubMed  Google Scholar 

  3. Kakavas S, Tiligada E. Hypothalamic histamine levels in hyperthyroid, arthritic and C48/80-treated rats. Inflamm Res. 2005;54:S30–S31.

    Article  CAS  PubMed  Google Scholar 

  4. Klecha AJ, Genaro AM, Gorelik G, Barreiro Arcos ML, Magali Silberman D, Schuman M, et al. Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway. J Endocrinol. 2006;189:45–55.

    Article  CAS  PubMed  Google Scholar 

  5. Karanikas G, John P, Wahl K, Schuetz M, Dudczak R, Willheim M. T-lymphocyte cytokine production patterns in nonimmune severe hypothyroid state and after thyroid hormone replacement therapy. Thyroid. 2004;14:488–92.

    Article  CAS  PubMed  Google Scholar 

  6. Botella-Carretero JI, Prados A, Manzano L, Montero MT, Escribano L, Sancho J, et al. The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal. Eur J Endocrinol. 2005;153:223–30.

    Article  CAS  PubMed  Google Scholar 

  7. Jiskra J, Antošová M, Límanová Z, Telicka Z, Lacinová Z. The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases. Clin Exp Immunol. 2009;156:211–6.

    Article  CAS  PubMed  Google Scholar 

  8. Nishimura M, Yamada K, Matsushita K, Sakamoto K, Saisu T, Kashiwabara H, et al. Changes in trough levels of whole blood cyclosporine and graft function of a kidney transplant recipient with onset of hypothyroidism after transplantation. Transplantation. 1996;62:1509–11.

    Article  CAS  PubMed  Google Scholar 

  9. Karga H, Papaioannou P, Venetsanou K, Papandroulaki F, Karaloizos L, Papaioannou G, et al. The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction. Eur J Endocrinol. 2000;142:236–42.

    Article  CAS  PubMed  Google Scholar 

  10. Michelis F, Tiligada E, Skaltsa H, Lazari D, Skaltsounis AL, Delitheos A. Effects of the flavonoid pilloin isolated from Marrubium cylleneum on mitogen-induced lymphocyte transformation. Pharm Biol. 2002;40:245–8.

    Article  CAS  Google Scholar 

  11. Balazs C and Farid NR. Effect of triiodothyronine on the short-lived and concanavalin-A generated suppressor T-cell functions. Clin Invest Med. 1984;7:157–60.

    Google Scholar 

  12. Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev. 2008;224:141–65.

    Article  CAS  PubMed  Google Scholar 

  13. Zhao X, Ye F, Chen L, Lu W, Xie X. Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25–CD45RA+ naive T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro. Cancer Sci. 2009;100:2143–51.

    Article  CAS  PubMed  Google Scholar 

  14. Tofani A, Sciuto R, Cioffi RP, Pasqualoni R, Rea S, Festa A, et al. Radioiodine-induced changes in lymphocyte subsets in patients with differentiated thyroid carcinoma. Eur J Nucl Med. 1999;26:824–9.

    Article  CAS  PubMed  Google Scholar 

  15. Tiligada E, Giannoulaki V, Pantos C. Hyperthyroidism induces conjunctival mast cell disruption without simultaneous modification of the early phase response to the histamine-releaser C48/80. Br J Pharmacol. 2003;138:82P.

    Google Scholar 

  16. Mihara S, Suzuki N, Wakisaka S, Suzuki S, Sekita N, Yamamoto S, et al. Effects of thyroid hormones on apoptotic cell death of human lymphocytes. J Clin Endocrinol Metab. 1999;84:1378–85.

    Article  CAS  PubMed  Google Scholar 

  17. Vacca RA, Moro L, Caraccio G, Guerrieri F, Marra E, Greco M. Thyroid hormone administration to hypothyroid rats restores the mitochondrial membrane permeability properties. Endocrinology. 2003;144:3783–8.

    Article  CAS  PubMed  Google Scholar 

  18. Nagy G, Koncz A, Perl A. T cell activation-induced mitochondrial hyperpolarization is mediated by Ca2+- and redox-dependent production of nitric oxide. J Immunol. 2003;171:5188–97.

    CAS  PubMed  Google Scholar 

  19. Castilho RF, Kowaltowskia AJ, Vercesia AE. 3, 5, 3′-Triiodothyronine induces mitochondrial permeability transition mediated by reactive oxygen species and membrane protein thiol oxidation. Arch Biochem Biophys. 1998;354:151–7.

    Article  CAS  PubMed  Google Scholar 

  20. Tiligada E. Chemotherapy: induction of stress responses. Endocr Relat Cancer. 2006;13:S115–24.

    Article  CAS  PubMed  Google Scholar 

  21. Zazueta C, Franco M, Correa F, García N, Santamaría J, Martínez-Abundisa E, et al. Hypothyroidism provides resistance to kidney mitochondria against the injury induced by renal ischemia-reperfusion. Life Sci. 2007;80:1252–8.

    Article  CAS  PubMed  Google Scholar 

  22. Chávez E, Zazueta C, Correa F, García N, Avilés C, Robles SG, et al. Modulation by substrates of the protective effect of cyclosporin A on mitochondrial damage. Life Sci. 2002;70:2413–20.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the University of Athens.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ekaterini Tiligada.

Additional information

Responsible Editor: Graham Wallace.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papaioannou, G., Michelis, F.V., Papamichael, K. et al. Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex vivo response to mitogen activation and cyclosporin A. Inflamm. Res. 60, 265–270 (2011). https://doi.org/10.1007/s00011-010-0264-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0264-7

Keywords

Navigation