CONTENTS OF THYROID HORMONES, CYTOKINES AND α2-MACROGLOBULIN IN BLOOD SERA AND IN CULTURE SUPERNATES OF BLOOD CELLS FROM THE GRAVES DISEASE PATIENTS
https://doi.org/10.15789/1563-0625-2015-1-53-58
Abstract
We had investigated levels of TTG, T4, TNFα, IL-6, IFNγ, and α2-MG in blood serum and supernates of short-term blood cultures in the patients with verified Graves disease before treatment and after reaching of euthyroid status, as compared with healthy controls. We have revealed that initial blood concentrations of free Т4 in the patients were increased, along with decrease in TSH, higher IL-6, IFNγ levels, as well as concentrations of α2-MG which participates in cytokine transport and synthesis. Thiamazole treatment normalized the hormonal profile and reduced blood levels of IL-6, IFNγ and α2-MG, however, without complete normalization, along with increase of serum TNFα contents. It was shown, that the patients before treatment had decreased in vitro response of cells to the mitogenic stimulation as shown by decreased induction of TNFα and IFNγ production, along with, increased spontaneous IFNγ levels. When reaching euthyroid state after Thiamazole administration, we observed an increased spontaneous IFNγ synthesis, decreased IL-6 production in resting cultures. In mitogen-stimulated cell cultures from the treated patients, IFNγ contents became normal, however, TNFα secretion remained lower than in controls. The α2-MG levels in supernates were stable and significantly lower, than in serum. We may presume that thyrotoxicosis treatment with Thiamazole causes stabilization of the endocrine state, however, being not sufficient for normalized production of cytokines, as well as α2-MG, with its regulatory and transporter functions, thus promoting recurrence of disease and reactivation of autoimmune events.
About the Authors
V. N. ZorinaRussian Federation
PhD, MD (Biology), Chief Research Associate, Research Laboratory of Immunology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
T. P. Maklakova
Russian Federation
PhD, MD (Medicine), Professor, Department of Endocrinology and Diabetology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
T. T. Sheppel
Russian Federation
Resident Physician, Department of Endocrinology and Diabetology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
O. N. Boyko
Russian Federation
Clinical Resident, Department of Endocrinology and Diabetology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
R. M. Zorina
Russian Federation
PhD, MD (Biology), Leading Research Associate, Research Laboratory of Immunology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
N. A. Zorin
Russian Federation
PhD, MD (Biology), Professor, Head, Research Laboratory of Immunology, Novokuznetsk State Institute of Postgraduate Medicine, Novokuznetsk, Russian Federation
References
1. Зорин Н.А., Зорина В.Н. Сигнальная система макроглобулинов. (Обзор литературы) // Биомедицинская химия, 2012. No 4. С. 400-410. [Zorin N.A., Zorina V.N. Signaling system of macroglobulins. Review. Biomeditsinskaya khimiya = Biomedical Chemistry, 2012, no. 4, pp. 400-410. (In Russ.)]
2. Baran P., Nitz R., Grötzinger J., Scheller J., Garbers C. Minimal interleukin 6 (IL-6) receptor stalk composition for IL-6 receptor shedding and IL-6 classic signaling. J. Biol. Chem., 2013, Vol. 288, no. 21, pp. 14756-14768.
3. Chávez-Tapia N.C., Rosso N., Uribe M., Bojalil R., Tiribelli C. Kinetics of the inflammatory response induced by free fatty acid accumulation in hepatocytes. Ann. Hepatol., 2013, Vol. 13, no. 1, pp. 113-120.
4. Li Y., Wang Z., Yu T., Chen B., Zhang J., Huang K., Huang Z. Increased expression of IL-37 in patients with Graves‘ disease and its ontribution to suppression of proinflammatory cytokines production in peripheral blood mononuclear cells. PLoS One., 2014, Vol. 16, no. 9, e107183.
5. Marzolo M.P., von Bernhardi R., Bu G., Inestrosa N.C. Expression of alpha(2)-macroglobulin receptor/ low density lipoprotein receptor-related protein (LRP) in rat microglial cells. J. Neurosci. Res., 2000, Vol. 60, no. 3, pp. 401-411.
6. Mikoś H., Mikoś M., Obara-Moszyńska M., Niedziela M. The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease (AITD). Endokrynol. Pol., 2014, Vol. 65, no. 2, pp. 150-155.
Review
For citations:
Zorina V.N., Maklakova T.P., Sheppel T.T., Boyko O.N., Zorina R.M., Zorin N.A. CONTENTS OF THYROID HORMONES, CYTOKINES AND α2-MACROGLOBULIN IN BLOOD SERA AND IN CULTURE SUPERNATES OF BLOOD CELLS FROM THE GRAVES DISEASE PATIENTS. Medical Immunology (Russia). 2015;17(1):53-58. (In Russ.) https://doi.org/10.15789/1563-0625-2015-1-53-58