TNF and brain inflammatory disease: In neuroinflammatory conditions, given that brain cytokines function as an integrated network [53], the increased expression of IL-18, probably modulated by TNF-α itself [54], could participate in perpetuating brain inflammation by stimulating the activation of the transcription factor NF-κB and the production of other pro-inflammatory mediators, such as IL-1β and TNF-α [55,56].