Taken together, our results demonstrate for the first time that, by promoting mROS generation, ethanol induces NLRP3/caspase-1 activation to trigger IL-1β/IL-18 production and cell death by pyroptosis and apoptosis, events that could contribute to neuroinflammation and brain damage induced by ethanol abuse. We further show crosstalk between NLRP3 and TLR4 since the elimination of TLR4 markedly diminishes ethanol actions on NLRP3 inflammasome activation and the production of the inflammatory cytokines IL-1β/IL-18. Our findings suggest that inflammasome activation may represent a new target in ethanol-induced neuroinflammation, and they support the potential role of IL-1Ra in the treatment of the neuropathological changes associated with alcohol abuse.
