Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1-mediated demyelinating disease of the central nervous system that serves as a model for multiple sclerosis (MS). There are several considerations that suggest a role for chemokines in the disease process. First, chemokines are highly expressed in the central nervous system with a tight temporal relationship to disease activity. Second, in vivo neutralization studies showed a distinct role for specific chemokines in the evolution of the process. Third, the selective and differential expression of chemokines in differing models of EAE bears a close relationship to the patterns of inflammatory pathology. Fourth, the spatial distribution of chemokine expression could plausibly contribute to lesion architecture. Finally, preliminary observations in MS material suggest that chemokine expression observed in EAE may provide useful information regarding the pathogenesis of inflammation in MS. We propose that temporal and spatial expression of chemokines are crucial factors, complementing adhesion molecule up-regulation, that regulate EAE disease activity.