Characterization of acute versus chronic relapsing autoimmune encephalomyelitis in DA rats

This study was undertaken to better understand the role of cytokines in the pathogenesis, especially in the mechanisms of relapse, of experimental aut oimmune encephalomyelitis (EAE). For this purpose, we induced acute and chr onic relapsing (CR) EAE in DA rats and determined several immunological par ameters in rats at various stages of two types of EAE. Histopathological an alysis revealed that there was no significant difference in the severity of inflammation in the spinal cord lesions between the two groups. However, d emyelination was observed only in rats with CR EAE. Cytokine analysis by co mpetitive PCR demonstrated that levels of TNF-alpha, IL-6 and IL-12 p40 mRN A in the spinal cord at the first attack of CR EAE were significantly highe r than those at the peak stage of acute EAE. The mRNA expression of anti-in flammatory cytokines, IL-10 and TGF-beta 1, was generally low in both acute EAE and the first attack of CR EAE and upregulated at later stages of CR E AE. These findings suggest that persistent high-level expression of pro-inf lammatory cytokines is closely associated with demyelination and relapse of EAE. In contrast, anti-inflammatory cytokines play only a minor role in th e relapse. (C) 2000 Elsevier Science B.V. All rights reserved.