Glucocorticoids exert opposing effects on macrophage function dependent on their concentration

Abstract

SummaryGlucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control the host's immune responses to pathogens. However, neither the role of hormone concentration nor the differential contribution of the glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities are known. Here we show that low levels of corticosterone enhance NO production as well as mRNA expression of pro-inflammatory cytokines, chemokines and enzymes required for mediator synthesis. In contrast, at high corticosterone concentrations macrophage function was strongly repressed. Importantly, inactivation of the GR by lentiviral delivery of siRNAs abrogated both the immunostimulatory and the immunosuppressive GC actions whereas inactivation of the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in vivo induced a preactivated state in macrophages that could be modulated by corticosterone. We conclude that GCs exert distinct effects on macrophage function dependent on their concentration, and that they primarily act through the GR despite concomitant expression of the MR.

Duality of liver and kidney lesions after systemic infection of immunosuppressed and immunocompetent mice withAspergillus fumigatus

“…In this respect it has been shown that high glucocorticoid concentrations reduce the production of nitric oxide, oxygen radicals and prostaglandins and impair phagocytosis. 19 Thus, such an impairment of function may allow the rapid germination of conidia. However, corticosteroids may also be responsible for the inflammation observed in the liver of treated animals.…”

Adipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase

“…MR is also expressed in nonepithelial cells, including cardiomyocytes (1), vascular cells (2,3) and macrophages (4,5), and has been implicated in pathological conditions such as heart failure, endothelial dysfunction, hypertension, insulin resistance, and obesity (6)(7)(8)(9)(10). Recently, MR has been identified in adipocytes (11)(12)(13)(14).…”

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

“…For example, even though expressed in macrophages, mineralocorticoid receptors do not seem to be involved in modulating immune cells function by GC. Instead, that action is strictly confined to the concentrationdependent binding of the GC to the GC receptors (Lim et al 2007). Nevertheless, it seems likely that a similar type of concentration-dependent effect of GC could be responsible for the difference in the effect of acute and chronic stress on the peripheral immune system, too (Sorrells and Sapolsky 2007).…”