Differential role of TNF-alpha and IFN-gamma in the brain of rats with chronic relapsing autoimmune encephalomyelitis

To elucidate the mechanisms of relapses of the clinical signs in experiment al autoimmune encephalomyelitis (EAE), the cytokine profile of chronic rela psing EAE (CR-EAE) in rats was determined by competitive polymerase chain r eaction (PCR). By immunization with guinea pig spinal cord homogenate and t reatment with low-dose cyclosporin A (CsA), rats developed two attacks of E AE with remission in between. Cytokine analysis revealed that the level of TNF-alpha mRNA increased at the first and second attacks with transient dis appearance at the remission phase. In contrast, the level of IFN-gamma mRNA was suppressed at the first attack by CsA and peaked at the second attack. Intraventricular administration of IFN-gamma prior to onset of disease sig ns induced more relapses, or a severe lethal form. In addition, the intrave ntricular injection of TNF-alpha caused the persistence of the clinical sig ns. These findings suggest that TNF-alpha contributes to the first and seco nd attacks of CR-EAE, while IFN-gamma is not required for the first attack but is closely related to the relapse of the disease. With regard to anti-i nflammatory cytokines, the levels of both TGF-beta 1 and IL-10 mRNA at the second attack were higher than those at the first attack. Taken together, d ifferential involvement of TNF-alpha and IFN-gamma is closely associated wi th the clinical features of CR-EAE. (C) 1999 Elsevier Science B.V. All righ ts reserved.