Contributions of cytokines to nonthyroidal illness

Purpose of reviewNonthyroidal illness is characterized by changes in thyroid hormone metabolism, such as decreased serum T3, increased serum rT3 and, during severe illness, diminished serum T4. Thyroid stimulating hormone remains unchanged or even decreases. Several mechanisms at various levels are involved in the observed changes in thyroid hormone metabolism although the pathogenesis is still incompletely understood. Nonthyroidal illness has been proposed as a useful adaptation mechanism of the body during illness and is viewed as part of the acute phase response. Cytokines are involved in the acute phase response and have the capacity to interfere with a variety of thyroid functions and to alter thyroid hormone metabolism in vitro and in vivo. Recent findingsSeveral inflammatory stimuli have proven to be suitable experimental models to study the pathogenesis of nonthyroidal illness. Inflammation leads to increased cytokine expression in organs involved in the regulation of the hypothalamus–pituitary–thyroid axis and the inflammatory response precedes changes in thyroid hormone metabolism. Both inhibiting and stimulating effects have been described in different organs and are probably mediated by cytokine-induced signal transduction pathways. SummaryThe differential effects of cytokines on thyroid functions suggest that cell-specific factors determine the final outcome of inflammatory stimuli on thyroid hormone metabolism.