What is the role of cytokines in the pathophysiology of euthyroid sick syndrome?

Updated: Oct 08, 2018
  • Author: Serhat Aytug, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

Cytokines are thought to play a role in NTI—particularly interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, and interferon-beta. Cytokines are thought to affect the hypothalamus, the pituitary, or other tissues, inhibiting production of TSH, thyroid-releasing hormone (TRH), thyroglobulin, T3, and thyroid-binding globulins. Cytokines are also thought to decrease the activity of type 1 deiodinase and to decrease the binding capacity of T3 nuclear receptors.

It has been proposed that several components of the thyroid hormone synthesis pathway are down-regulated by cytokines directly on the level of thyrocyte, eventually leading to decreased secretion of T4 and T3. [3]

Interferon-gamma has various effects on human thyrocytes in culture. Interferon-gamma was shown to inhibit TSH-induced thyroid hormone and thyroglobulin secretion, TSH-induced thyroglobulin mRNA expression, TSH-induced thyroid peroxidase expression, and TSH- and cAMP-induced up-regulation of TSH receptors on thyroid cells. Interferon-gamma was also demonstrated to inhibit the TSH-induced increase in sodium-iodide symporter (NIS) expression in rat FTRL-5 cells, leading to diminished iodide uptake. In addition, overexpression of interferon-gamma in thyroid cells in a transgenic mouse leads to primary hypothyroidism due to a significant decrease in NIS mRNA and protein expression.

TNF-alpha is known to inhibit TSH-induced cAMP response thyroglobulin production and release in cultured thyrocytes. TNF-alpha also inhibits NIS expression in rat FTRL-5 cells. Cytokines were also shown to inhibit type 1 deiodinase expression and activity in rat thyrocyte and FRTL-5 cells. [4]


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