Cytokines and thyroid function

Cytokines play a crucial role in autoimmune thyroid disease (ATD) through various mechanisms. They are produced in the thyroid by intrathyroidal inflammatory cells, in particular lymphocytes, as well as by the thyroid follicular cells (TFC) themselves and may thus act in a cascade to enhance the autoimmune process (Fig.l). Cytokines upregulate the inflammatory reaction through stimulation of both T and B cells, resulting in antibody production and tissue injury. In addition, intrathyroidal cytokines induce immunological changes in TFC including enhancement of both major histocompatibility complex (MHC) class I and class II molecule expression, and upregulation of adhesion and complement regulatory molecule expression. Cytokines can also modulate both growth and function of TFC and have a role in extrathyroidal complications of ATD, most importantly thyroid-associated ophthalmopathy (TAO), where they induce fibroblast proliferation and enhance the production of glycosaminoglycans (GAG), resulting in proptosis and the other clinical features of the disease. In addition to these effects, exogenous administration of cytokines has been associated with impairment of thyroid function ranging from the appearance of autoantibodies