The canonical pathways for induction of IL-1β include both a priming step, mediated by TLR4, as well as P2X7 receptor-activation of the inflammasome to process pro-IL-1β. It is currently not known if stress rapidly increases an endogenous activator of TLR4 that increases transcription. Alternatively, it is possible that there is a basal level of readily available pro-IL-1β that could be converted to IL-1β and released. The latter possibility is supported by studies demonstrating that IL-1β is involved in cellular models of learning and memory (Goshen et al., 2007; Labrousse et al., 2009), indicating pro-IL-1β is present and readily available for processing and release under physiological conditions. Additional studies are required to further characterize the mechanisms underlying the rapid release of IL-1β in response to acute, as well as chronic stress.
