CYTOKINES AND THYROID-FUNCTION

Cytokines play a crucial role in autoimmune thyroid disease (ATD) thro ugh various mechanisms. They are produced in the thyroid by intrathyro idal inflammatory cells, in particular lymphocytes, as well as by the thyroid follicular cells (TFC) themselves and may thus act in a cascad e to enhance the autoimmune process (Fig.1). Cytokines upregulate the inflammatory reaction through stimulation of both T and B cells, resul ting in antibody production and tissue injury. In addition, intrathyro idal cytokines induce immunological changes in TFC including enhanceme nt of both major histocompatibility complex (MHC) class I and class II molecule expression, and upregulation of adhesion and complement regu latory molecule expression. Cytokines can also modulate both growth an d function of TFC and have a role in extrathyroidal complications of A TD, most importantly thyroid-associated ophthalmopathy (TAO), where th ey induce fibroblast proliferation and enhance the production of glyco saminoglycans (GAG), resulting in proptosis and the other clinical fea tures of the disease. In addition to these effects, exogenous administ ration of cytokines has been associated with impairment of thyroid fun ction ranging from the appearance of autoantibodies done to the develo pment of frank thyroid dysfunction. Cytokines have also been implicate d in subacute thyroiditis (SAT) and amiodarone-induced thyroid dysfunc tion, as well as in thyroid function abnormalities occurring in patien ts with nonthyroidal illnesses (NTI). Genetic variations in cytokine g enes represent potential risk factors for ATD, and disease association s have been described for polymorphisms in IL-1ra and TNF beta genes. Recent experimental evidence suggests the possibility of novel cytokin e-based therapeutic approaches for ATD and its complications, in parti cular TAO. (C) 1997 Elsevier Science Ltd.