High IL-6 and low IL-10 in the central nervous system are associated with protracted relapsing EAE in DA rats.
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for multiple sclerosis (MS). The mechanisms behind differences in clinical course of EAE in different rat strains have not been defined. We induced acute EAE in Lewis rats and protracted relapsing EAE (PR-EAE) in DA rats and examined mRNA expression of IL-1 beta, IL-6, IL-10, IL-12, and TNF-beta in brain tissue sections, cerebrospinal fluid (CSF) cells, and lymph node cells. IL-1 beta, IL-12 and TNF-beta mRNA expression in brain tissue sections appeared early and peaked at the height of clinical signs in both acute and PR-EAE, consistent with a disease-promoting role for these cytokines. High levels of IL-6 mRNA-expressing cells were present in CNS and lymph node cells in PR-EAE, while almost absent in acute EAE. In contrast, IL-10 was very low in PR-EAE but strongly expressed in acute EAE, in particular during clinical recovery. Regulatory changes of IL-6 and IL-10 both systemically and within the CNS, but with temporal differences between compartments, seem pivotal for development of PR-EAE in DA rats. These findings could have relevance for pathogenesis and treatment of MS.
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Zhu
J
J
Xiao
B G
BG
Mustafa
M
M
Link
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H
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D001923:Brain Chemistry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis* / Q000134:cerebrospinal fluid; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis* / Q000134:cerebrospinal fluid; D008198:Lymph Nodes / Q000737:chemistry; D008233:Lymphotoxin-alpha / Q000032:analysis; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013045:Species Specificity
D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12