Dose-response immunomodulatory effects of glucocorticoid on gene expression of cytokine and stress hormone receptors in human PBMC (57.18)

Abstract

Abstract Previous studies demonstrate Th1/Th2 cytokine balance is altered with stress hormone equivalent dexamethasone (Dex) levels in human PBMC cultures. The modulatory effects of Dex on gene expressions of FoxP3, IFN-γ receptors (IFN-γR), IL-4 receptors (IL-4R), glucocorticoid receptors (GR), and beta 2 adrenergic receptors (β2AR) were investigated. PBMC from 17 normal humans were cultured with 10-7, 10-8, or 10-9M Dex (mimics high, low, and non stressed states) for 24 hrs (short term) and 11 days (long term). Gene expression changes were assessed by real-time PCR. Results showed mRNA expressions of FoxP3, GR and IL-4R were decreased, whereas β2AR and IFN-γ R were upregulated with various concentrations of Dex (24 hrs). After 11 days, FoxP3 level remained down-regulation, whereas GR and β2AR levels returned to control levels in all cultures. In contrast, IL-4R expression increased (11 days) in all Dex concentrations. This resulted in decreased IFN-γR/IL-4R from 24 hrs (favoring Th1) to 11 days (favoring Th2) with Dex. This suggests that short term Dex exposure (acute stress) can initiate immunoregulatory reactions (i.e. Th1 based) that may be protective against many infectious challenges, possibly through a down-regulation of GR resulting in less suppressive effects of steroids and increased sensitivity to catecholamines. Longer term Dex exposure (chronic stress) may ultimately alter host response resulting in increased susceptibility to infections and/or hypersensitivity states.