title: Differential role of TNF-alpha and IFN-gamma in the brain of rats with chronic relapsing autoimmune encephalomyelitis.
abstract: To elucidate the mechanisms of relapses of the clinical signs in experimental autoimmune encephalomyelitis (EAE), the cytokine profile of chronic relapsing EAE (CR-EAE) in rats was determined by competitive polymerase chain reaction (PCR). By immunization with guinea pig spinal cord homogenate and treatment with low-dose cyclosporin A (CsA), rats developed two attacks of EAE with remission in between. Cytokine analysis revealed that the level of TNF-alpha mRNA increased at the first and second attacks with transient disappearance 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 signs induced more relapses, or a severe lethal form. In addition, the intraventricular injection of TNF-alpha caused the persistence of the clinical signs. These findings suggest that TNF-alpha contributes to the first and second 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-inflammatory cytokines, the levels of both TGF-beta1 and IL-10 mRNA at the second attack were higher than those at the first attack. Taken together, differential involvement of TNF-alpha and IFN-gamma is closely associated with the clinical features of CR-EAE.
authors.affiliation: Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan. nata@tmin.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Tanuma
authors.forename: T
authors.initials: T
authors.lastname: Shin
authors.forename: K
authors.initials: K
authors.lastname: Kogure
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D002908:Chronic Disease; D016572:Cyclosporine / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007276:Injections, Intraventricular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D013116:Spinal Cord / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D016572:Cyclosporine