Role of Endogenous Glucocorticoids in Immune System Function: Regulation and Counterregulation

Abstract

The sections in this article are: In Vivo Versus in Vitro Glucocorticoids Natural Versus Synthetic Glucocorticoids Corticosteroid Receptor Subtypes Corticosteroid‐Binding Globulin Physiological Versus Nonphysiological Concentrations of Glucocorticoids Factors Regulating Immune Cell Exposure to Glucocorticoids Factors in the Absence of Immune Challenge Factors in the Presence of Immune Challenge Direct Effects of Glucocorticoids on Immune Cells Molecular Features of Intracellular Glucocorticoid Receptors Regulatory Effects of Glucocorticoids on the Expression of Immunologically Important Genes Possible Alternative Mechanisms of Glucocorticoid Action Strategies for Assessing the Role of Endogenous Glucocorticoids in Immune System Function Circadian Studies Stress Studies In Vivo Secretagogue Stimulation Studies Adrenalectomy and Glucocorticoid Replacement Studies Other More Selective Manipulations of Glucocorticoid Action Glucocorticoid Effects on Immune Subsystems Immune Cell Maturation, Differentiation, and Turnover Immune Cell Trafficking Inflammation Septic Shock T helper 1 and T helper 2 Response Antibody Production Cytotoxicity and Delayed Type Hypersensitivity General Models of Glucocorticoid Regulation of the Immune System Counterregulatory Role of Glucocorticoids Regulatory Role of Glucocorticoids Regulatory Role of Glucocorticoids During Stress Bidirectional Regulatory Effects of Glucocorticoids

Intracellular glucocorticoid receptors in spleen, but not skin, vary seasonally in wild house sparrows (Passer domesticus)

“…Acute increases in plasma CORT titres were traditionally thought to be primarily immunosuppressive, but they can also play immune-enhancing roles [2]. The effect seen may depend on which component of the immune system is being examined [5], seasonal variation in circulating CORT titres [6] and the time scale of CORT activation [7]. For example, a short-term rise in CORT due to acute stress can increase delayed-type hypersensitivity (DTH) reactions, enhancing the reallocation of immune cells from spleen and bone marrow into more peripheral locations, such as skin, whereas sustained high CORT can suppress DTH [8,9].…”

“…In fact, because CORT's effects on immune function are so heterogeneous, Spencer et al [5] suggest that it is not helpful to try to describe a single unitary role for CORT on the immune system. Rather, they encourage thinking about CORT function at a number of different physiological levels, such as at the level of different immune tissues.…”

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)

“…At baseline concentrations, CORT helps regulate metabolism, activity levels and feeding behavior; at the higher concentrations caused by a stressor, CORT is an essential component of the vertebrate stress response (Landys et al, 2006;Sapolsky et al, 2000). During the stress response, CORT helps animals mobilize energy stores, enhances certain immune components and promotes escape and selfmaintenance behaviors (Spencer et al, 2001;Wingfield and Kitaysky, 2002). …”

Immune response to aTrichinella spiralisinfection in house mice from lines selectively bred for high voluntary wheel running

“…As we expected, among infected animals, IgE levels were significantly lower in HR mice than in C mice. Assuming general immunosuppressive effects of CORT (Sapolsky et al, 2000;Galon et al, 2002;Spencer et al, 2011) and our hypothesis that HR mice would allocate less energy toward immune upregulation, a smaller increase in IgE levels among HR mice appears to be a reasonable response to infection. However, the effects of glucocorticoids on the immune system are complex.…”

“…However, the effects of glucocorticoids on the immune system are complex. Despite an enormous number of studies, the extent to which glucocorticoids influence innate versus acquired immune function or humoral versus cell-mediated responses is not clear (for a review, see Spencer et al, 2011). In addition to being part of a general immune response to parasites, IgE is thought to bind directly to T. spiralis and directly aid in expulsion of the parasite from the gut of the host, and there is evidence that IgE may also help kill larval stages of T. spiralis (Gurish et al, 2004).…”