Effects of proinfl ammatory cytokines on intracellular glucocorticoid metabolism

概要

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Cytokines is known to infl uence hormone synthesis and secretion. Indeed, some of the proinfl ammatorycytokines stimulate hormone release at the hypothalamic, pituitary, and peripheral endocrine organs. Recently, a newparadigm of immune-endocrine interaction has been emerging. We and others have shown that cytokines modify theeff ectiveness of hormone action. This is occurring via enhancement of receptor-mediated signaling, or modifi cation ofintracellular metabolism of hormones. In the latter case, we found that representative cytokines such as interleukin 1βand TNFα stimulate the expression of the glucocorticoid-activating enzyme 11β- ~ hydroxysteroid dehydrogenase type1（ 11βHSD1） and suppress that of the inactivating enzyme 11βHSD2, thus increasing the intracellular concentrationand action of glucocorticoids. In vascular smooth muscle cells, this mechanism is advantageous in preventing vascularcollapse during sepsis. We also found that, in hepatocytes, cytokines suppress the expression of the thyroid hormoneactivatingenzyme 5’-deiodinase type I. This may be responsible for the low T3 syndrome in critical illness.
弘前大学の論文