The EAE-associated behavioral syndrome: I. Temporal correlation with inflammatory mediators

To elucidate the mechanisms underlying the EAE-associated behavioral syndrome (EBS), we examined the temporal correlation between the behavioral alterations and inflammatory processes. Onset of the behavioral syndrome was associated with the onset of brain infiltration, as well as mRNA expression of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) and elevated production of interleukin 1β protein and prostaglandin E₂ (PGE₂). Sickness behavior symptoms coincided with peak cytokine expression. Behavioral recovery was associated with a reduction of cytokine expression, but not infiltration, PGE₂ production or motor disturbances. These results suggest that inflammatory processes in general, and the production of pro-inflammatory cytokines in particular, are involved in mediating EAE-associated sickness behavior.