Cytokine actions on the thyroid gland.

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.