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Cytokine actions on the thyroid gland
1Department of Endocrionology, H:S Frederiksberg Hospital.
Insights
Cytokines like IL-1 influence thyroid cell function, with some inhibiting activity and others playing roles in immune responses and thyroid disease pathogenesis. Understanding these cytokine effects is key to managing thyroid conditions.
Area of Science:
- Endocrinology
- Immunology
- Cell Biology
Background:
- Cytokines are crucial for immune response regulation.
- Their influence on the thyroid gland is significant in both health and disease.
Purpose of the Study:
- To review the impact of key cytokines on the thyroid gland in various models and humans.
- To investigate the functional effects of cytokines on isolated human thyrocytes.
Main Methods:
- Review of existing literature on cytokine effects in animal models and humans.
- In vitro study using monolayer cultures of human paraadenomatous thyroid cells.
- Analysis of cytokine-induced changes in thyroid cell function, including nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) release, and effects on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) release.
Main Results:
- Interleukin-1 (IL-1) demonstrated a biphasic, non-cytotoxic, and reversible effect on thyroid cell function.
- Moderate to high concentrations of IL-1, tumor necrosis factor (TNF), and interferon-gamma (IFN-gamma) inhibited thyroid cell function.
- IL-1 stimulated NO and cGMP release, inhibited adenylate cyclase pathways, and stimulated guanylate cyclase pathways, with effects counteracted by IL-1 receptor antagonist (IL-1ra).
Conclusions:
- Cytokines predominantly inhibit the hypothalamic-pituitary-thyroid axis.
- Cytokines may contribute to the euthyroid sick syndrome and autoimmune thyroid diseases (AITD).
- Further research into cytokine actions is vital for understanding the endocrine system and managing thyroid disorders.
Abstract:
Cytokines are integral components of the complex intercellular communication required to mount and control an immune response. The purpose of this review is to describe the influence of the most important cytokines on the thyroid gland in animal models and in humans and on isolated thyroid cells. We have used an in vitro system of monolayer cultures of human paraadenomatous thyroid cells for the study of the phenomenological actions of cytokines on the function of the thyrocytes. A biphasic, non-cytotoxic and reversible influence of IL-1 supporting a role of IL-1 in the physiological regulation of thyroid cell function was found. IL-1 in moderate to high concentrations and TNF and IFN-gamma all inhibited thyroid cell function. IL-1 induced release of NO and cGMP from the thyrocytes, but an inhibitor of nitric oxide synthase did not abolish the IL-1-induced inhibition of the release of Tg and cAMP from the TEC. The biochemical pathways by which IL-1 influences thyrocytes are not fully clarified. IL-1 beta inhibited the adenylate cyclase mediated pathways and stimulated the guanylate cyclase mediated pathways, and all the demonstrated IL-1 effects were counteracted by IL-1 ra indicating, that the effects were exerted through activation of specific IL-1 receptors on thyrocytes. The predominant effect of cytokines on the hypothalamic-pituitary-thyroid axis is inhibitory and the cytokines may play a role during physiological as well as pathophysiological conditions contributing to the euthyroid sick syndrome and AITD. A model for the pathogenesis of AITD is outlined. The trigger, of the autoimmune process in AITD is unknown. However, the earliest steps include the interaction between antigen presenting cells and Th cells. In the later phase antigen specific and non-specific immune cells are recruited to the thyroid and an inflammatory infiltrate is built. During this process inflammatory mediators including cytokines, free nitric and oxygen radicals are released. A better understanding of pathogenetic mechanisms is crucial for an appropriate and effective management of AITD, and if possible, for its prevention. Further studies of the actions of these potent agents are one of the keys to a better understanding of the endocrine system both in health and in disease.