The current model of HPA axis-immune system interactions involves glucocorticoid potentiation of the innate immune system and repression of the adaptive immune system (Busillo and Cidlowski 2013). All immune cells express GR at some state of activation, which allows glucocorticoids to have selective, dose-dependent effects on various aspects of immunity such as proliferation of memory T cells (Gutsol, Sokhonevich et al. 2013), macrophage numbers (Zheng, Zhong et al. 2013), and expression of TLRs (Jin, Qin et al. 2009). Impact of glucocorticoids is mediated through changes in gene expression where glucocorticoid/GR complexes bind to specific DNA sequences, called glucocorticoid response elements (GREs), tethered by transcription factors NFκB, AP1, STAT3, and STAT5 (Chinenov and Rogatsky 2007). For instance, glucocorticoids modulate TLR signaling by affecting: 1) downstream protein kinases, 2) suppressors of cytokine signaling (SOCS), 3) GR-inducible leucine zipper protein, and 4) GR-mediated increased expression of TLRs (Chinenov and Rogatsky 2007). In addition to TLR-mediated regulation, GR activity up-regulates the activity of NLRP3, a NOD-like receptor (NLR) involved in the production of IL-1β (Busillo, Azzam et al. 2011). Humans under various stressful environments
