The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNFα-induced sickness behavior

Rationale During the course of an infection, the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) acts in the brain to trigger development of behavioral responses, collectively termed sickness behavior. Biological activities of TNFα can be mediated by TNF receptor type 1 (TNF-R1) and type 2 (TNF-R2). TNFα activates neutral sphingomyelinase through the TNF-R1 adapter protein FAN (factor associated with neutral sphingomyelinase activation), but a behavioral role of FAN in the brain has never been reported.