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Published in: Inflammation Research 3/2011

01-03-2011 | Original Research Paper

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

Authors: Garyphallia Papaioannou, Fotios V. Michelis, Konstantinos Papamichael, Helen Karga, Ekaterini Tiligada

Published in: Inflammation Research | Issue 3/2011

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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.
Literature
1.
go back to reference 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.PubMed 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.PubMed
2.
go back to reference 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.PubMed 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.PubMed
3.
go back to reference Kakavas S, Tiligada E. Hypothalamic histamine levels in hyperthyroid, arthritic and C48/80-treated rats. Inflamm Res. 2005;54:S30–S31.CrossRefPubMed Kakavas S, Tiligada E. Hypothalamic histamine levels in hyperthyroid, arthritic and C48/80-treated rats. Inflamm Res. 2005;54:S30–S31.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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. 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.
12.
go back to reference Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev. 2008;224:141–65.CrossRefPubMed Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev. 2008;224:141–65.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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. 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.
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.PubMed 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.PubMed
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex vivo response to mitogen activation and cyclosporin A
Authors
Garyphallia Papaioannou
Fotios V. Michelis
Konstantinos Papamichael
Helen Karga
Ekaterini Tiligada
Publication date
01-03-2011
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 3/2011
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-010-0264-7

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