Effects of Glucocorticoids in the Immune System

Abstract

Glucocorticoids (GCs) are steroid hormones with widespread effects. They control intermediate metabolism by stimulating gluconeogenesis in the liver, mobilize amino acids from extra hepatic tissues, inhibit glucose uptake in muscle and adipose tissue, and stimulate fat breakdown in adipose tissue. They also mediate stress response. They exert potent immune-suppressive and anti-inflammatory effects particularly when administered pharmacologically. Understanding these diverse effects of glucocorticoids requires a detailed knowledge of their mode of action. Research over the years has uncovered several details on the molecular action of this hormone, especially in immune cells. In this chapter, we have summarized the latest findings on the action of glucocorticoids in immune cells with a view of identifying important control points that may be relevant in glucocorticoid therapy.

The triterpene echinocystic acid and its 3-O-glucoside derivative are revealed as potent and selective glucocorticoid receptor agonists

“…Besides, by physical interaction of GR with other transcription factors, such as NF-κΒ, cortisol negatively regulates the expression of many inflammatory cytokines, which constitute NF-κΒ target genes (Liberman et al, 2007;Psarra and Sekeris, 2008). Thus, cortisol affects human metabolism as well as human immune responses (Bamberger et al, 1996;Dostert and Heinzel, 2004;Degawa-Yamauchi et al, 2005;Wang, 2005;Rose and Herzig, 2013;Oppong and Cato, 2015). Due to the anti-inflammatory actions of cortisol, GCs as well as synthetic glucococorticoids, are widely used in medicine to treat inflammatory diseases and autoimmune disorders (Buttgereit et al, 2015).…”

Different response to glucocorticoid therapy in autoimmune diseases of CNS

“…IL-1β, IL-6, TNF-α), while enhancing the expression of anti-inflammatory cytokines (e.g. IL-10,T-GF-β), T-cell apoptosis and redistribution, a shift in the population of Th cells from Th1 to Th2 and the proportion of regulatory cells (12).…”

“…Since ample evidence indicates that GCs differentially regulate the production of Th1 and Th2 cytokines (12) it is important to know how GCs affect the production of IL-17, a cytokine accused to be critically involved in the pathogenesis of autoimmune and chronic inflammatory diseases frequently treated with GCs. Therefore, the aim of my thesis (13) was to analyze effects of methylprednisolone (MP), a synthetic glucocorticoid drug on IL-17 expression and production, and compare these effects with corresponding effects on IFN-γ.…”

“…It suggests that action of MP on IL-17 generation in rat LNC includes both direct influence on T cells and indirect influence on other LNC populations contributing to T cells IL-17 production (14). Indeed, MP was shown to affect activity of accessory LNC cells, including dendritic cells and macrophages which produce numerous cytokines that are important for the stimulation of IL-17 in T cells, such as IL-1, TNF-α, IL-6, IL-18 (12).…”

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

“…7 Once cortisol is released, it binds to glucocorticoid receptors on target cells, altering gene transcription [8][9][10] and regulating multiple physiological functions, including cellular metabolism of glucose, proteins, and lipids 11,12 for energy homeostasis, 13,14 salt and water balance, 15 blood pressure, 16,17 and functions of the immune system. 18,19 Abnormal activity of the adrenal cortex leads to hypercortisolism or 60% of Cushing's syndrome cases, characterized by excessive cortisol levels. Cushing's syndrome is a rare disease with an incidence of 1.2-1.7 per million people a year.…”