This review focuses on the role of the inflammasome and IL-1β in depression for several reasons. First, inflammatory cytokines such as IL-1β are elevated in depression, and second, activate the HPA axis, which is dysregulated in depressed patients. Third, chronic inflammatory diseases like rheumatoid arthritis and diabetes that have high rates of comorbidity with depression also activate the NLRP3 inflammasome complex (Evans et al., 2005; Mason et al., 2012). Fourth, we have found that blockade of IL-1β is sufficient to block depressive behavioral and cellular responses resulting from exposure to chronic stress (Koo et al., 2008). Fifth, we hypothesize that IL-1β is the first step in the pro-inflammatory response to psychological stress and results in a cascade of inflammatory cytokine responses. Each of these points is discussed in detail in this section.
