Alcohol has a potent activating effect on the HPA axis as well as on neuroimmune signaling; therefore, these effects may integrate the responses of the central nervous system (CNS) to alcohol and stress (figure 6). For example, TNF-α, IL-1β, and IL-6 act upon the HPA axis and SNS, both directly via local effects and indirectly via the CNS (Besedovsky and del Rey 1996; Pickering et al. 2005; Wilder 1995). Furthermore, CRH has a variety of complex effects on immune cells (Elenkov et al. 1999) and modulates immune/inflammatory responses through receptor-mediated actions of glucocorticoids on anti-inflammatory target immune cells (Tsigos and Chrousos 2002). In contrast, elevated glucocorticoid levels in the prefrontal cortex are proinflammatory, potentiating LPS–TLR4 activation of NF-κB and other proinflammatory signals (Munhoz et al. 2010). The neuro-transmitter norepinephrine that is released by SNS activation also disturbs inflammatory cytokine networks and innate immune-cell function. Similarly, the hypothalamic peptide β-endorphin (BEP), whose release is stimulated by CRH during HPA activation, can inhibit stress-hormone production and activate peripheral immune functions (Sarkar and Zhang 2013). All of these findings suggest that the stress–HPA
