Chunk #11 — 5. Inflammasome is a key mediator of stress, depression and comorbid illnesses — 5.2. Inflammatory cytokines and dysfunction of the HPA axis
Inflammatory cytokines are potent activators of the HPA axis (Berkenbosch et al., 1987; Sapolsky et al., 1987)(Fig 3), which is elevated in depressed patients, possibly due in part to increased levels of IL-1β (Turnbull and Rivier, 1999). A recent large meta-analysis (354 studies, 18,374 individuals) found that approximately 73% of depressed individuals had elevated cortisol values compared to nondepressed individuals (Stetler and Miller, 2011). IL-1β increases the release of hypothalamic corticotropin-releasing hormone (CRH), secretion of pituitary adrenocorticotropic hormone (ACTH), and adrenal steroidogenesis (Fig. 3) (Berkenbosch et al., 1987; Maes et al., 1993; Sapolsky et al., 1987; Tominaga et al., 1991), effects that are thought to occur via indirect mechanisms (Hsieh et al., 2010) (Goshen and Yirmiya, 2009).
