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.
Similar content being viewed by others
References
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.
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.
Kakavas S, Tiligada E. Hypothalamic histamine levels in hyperthyroid, arthritic and C48/80-treated rats. Inflamm Res. 2005;54:S30–S31.
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.
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.
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.
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.
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.
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.
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.
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.
Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev. 2008;224:141–65.
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.
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.
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.
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.
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.
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.
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.
Tiligada E. Chemotherapy: induction of stress responses. Endocr Relat Cancer. 2006;13:S115–24.
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.
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.
Acknowledgments
This work was financially supported by the University of Athens.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible Editor: Graham Wallace.
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-010-0264-7