Recently emerging evidence that the NF-kappa B family plays an important role in autoimmune disease has produced very broad and sometimes paradoxical conclusions. In the present study, we elucidated that the activation of RelA (p65) of NF-kappa B and I kappa B dissociation assumes a distinct role in experimental autoimmune encephalomyelitis (EAE) progression by altering I kappa B phosphorylation and/or degradation. In the present study of factors that govern EAE, the presence and immunoreactivity of nuclear RelA and phospho-I kappa B were recorded at the initiation and peak stage, and degradation of I kappa B alpha progressed rapidly at an early stage then stabilized during recovery. The immunoreactivity to RelA and phospho-I kappa B occurred mainly in inflammatory cells and microglial cells but only slightly in astrocytes. Subsequently, the blockade of la dissociation from NE-kappa B reduced the severity of disease by decreasing antigen-specific T cell response and production of IL-17 in EAE. Thus, blocking the dissociation of I kappa B from NF-kappa B can be utilized as a strategy to inhibit the NP-kappa B signal pathway thereby to reduce the initiation, progression, and severity of EAE. (C) 2011 Elsevier Inc. All rights reserved.