As discussed above in the gene expression studies, the mechanisms by which ethanol exerts dose-dependent effects on the immune system could also include modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which tightly regulates the stress response, in turn affecting immunity. Response to different stressors is mediated by several neural circuits that converge on the paraventricular nucleus (PVN) of the hypothalamus (Myers, McKlveen et al. 2014). The PVN regulates pituitary hormone production, including adrenocorticotropic hormone (ACTH), which binds to melanocortin type 2 receptors in the adrenal cortex to induce steroidogenesis in distinct layers (Dringenberg, Schwitalla et al. 2013). Primates have a threelayer adrenal cortex with cortisol being the primary glucocorticoid produced in the zona fasciculata (Nguyen and Conley 2008), which is released in response to stress (O'Connor, O'Halloran et al. 2000). Corticosterone is the main glucocorticoid involved in the regulation of stress responses in rodents (Smith and Vale 2006).
