Immunomodulatory effects of dexamethasone on gene expression of cytokine and stress hormone receptors in peripheral blood mononuclear cells.

Glucocorticoid (GC) such as cortisol in humans is a major stress hormone and can influence immunomodulation through various mechanisms including impact on regulatory T-cell (RTC) elements and changes in Th1/Th2 cytokine balance. In this study, we sought to determine the immunomodulatory effects of GC equivalent dexamethasone (DEX) at various concentrations (10(-7), 10(-8), and 10(-9) M) on gene expression of RTC, cytokine receptors and stress hormone receptors from normal human peripheral blood mononuclear cells (PBMC) in an in vitro stress model in 24 h (acute stress) vs 11-day (chronic stress) cultures. Results revealed that the mRNA of forkhead box P3 (FoxP3) was significantly decreased at 24 h with 10(-7) and 10(-8) M DEX. After 11 days, FoxP3 expression in the 10(-8) M DEX cultures had returned to baseline but was still down-regulated with 10(-7) M DEX. GC receptor (GR) mRNA decreased and β2 adrenergic receptor (β 2AR) mRNA increased significantly after 24 h exposure to DEX. These changes had returned to baseline in the 11-day cultures. The IFN-γR/IL-4R ratio, an alternative marker for Th1/Th2 balance, was significantly increased at 24 h and decreased after 11-day cultures with 10(-7) and 10(-8) M DEX compared to control cultures. These findings further contribute to our understanding of the mechanisms associated with the effects of acute vs. chronic stress on normal immune balance.