Title:Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis
Volume: 14
Issue: 7
Author(s): Christopher Bolton and Paul Smith
Affiliation:
Keywords:
Acute inflammation, EAE-targeted drugs, endothelial cells, experimental autoimmune encephalomyelitis, mast
cells, microglia, multiple sclerosis, neutrophils, platelets.
Abstract: The primary pathology of the human central nervous system disease multiple sclerosis (MS)
and the animal counterpart experimental autoimmune encephalomyelitis (EAE) includes
immunological and inflammatory events. Immune system involvement in MS has been widely debated
but the role of inflammation has received less attention. Classic acute inflammation features vasculitis,
resident tissue macrophage and mast cell participation plus the involvement of circulatory-derived
neutrophils and platelets. Pre-lesion development in MS incorporates cerebral vasculitis, activated
resident microglia in normal appearing white matter together with infiltrating cell types and factors indicative of an acute
inflammatory reaction. Similarly, the formation of perivascular lesions during early EAE includes characteristic
neurovasculitis, the participation of central nervous system microglial phenotypes plus haemopoietic cells and mediators,
signifying an ongoing acute inflammatory response. EAE has been extensively used as a screen to select drugs for MS
treatment but has been criticised as unrepresentative of the human condition due to fundamental differences in disease
induction and pathogenesis. The review provides compelling evidence for a distinct acute inflammatory phase in MS
lesion formation that is convincingly reproduced in early EAE pathology. Moreover, consideration of drug efficacy
studies undertaken during initial EAE validates the occurrence of an acute inflammatory phase in disease pathogenesis.
Critical appraisal, recognition and acceptance of the mutual acute inflammatory components inherent in the primary
pathology of MS and EAE reveals new targets and encourages confident and reliable employment of the animal model in
the assessment of novel compounds for the control of key primary pathological events in human demyelinating disease.
