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 autoimmune encephalomyelitis (EAE). For this purpose, we induced acute and chronic relapsing (CR) EAE in DA rats and determined several immunological parameters in rats at various stages of two types of EAE. Histopathological analysis revealed that there was no significant difference in the severity of inflammation in the spinal cord lesions between the two groups. However, demyelination was observed only in rats with CR EAE. Cytokine analysis by competitive PCR demonstrated that levels of TNF-alpha, IL-6 and IL-12 p40 mRNA in the spinal cord at the first attack of CR EAE were significantly higher than those at the peak stage of acute EAE. The mRNA expression of anti-inflammatory cytokines, IL-10 and TGF-beta1, was generally low in both acute EAE and the first attack of CR EAE and upregulated at later stages of CR EAE. These findings suggest that persistent high-level expression of pro-inflammatory cytokines is closely associated with demyelination and relapse of EAE. In contrast, anti-inflammatory cytokines play only a minor role in the relapse.
Tanuma
N
N
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, 183-8526, Tokyo, Japan.
Shin
T
T
Matsumoto
Y
Y
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma