title: IL-10 suppresses experimental autoimmune neuritis and down-regulates TH1-type immune responses.
abstract: Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic inflammatory disorder of the peripheral nervous system (PNS). Cellular mechanisms, including macrophage and T cell infiltration, and cytokines like IFN-gamma and TNF-alpha are intimately involved in the pathogenesis of EAN. Interleukin 10 (IL-10) is a TH2-type cytokine that suppresses monocyte and TH1 cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in EAN. When administered from the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shortened clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppressed the severity of EAN. Pheripheral nerve myelin antigen-reactive IFN-gamma-secreting TH1-like cells were decreased in lymph nodes from IL-10-treated compared to control EAN rats. PNS autoantigen-induced T cell proliferation and B cell responses were not affected. P2 protein-reactive IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 mRNA-expressing lymph node cells were also downregulated in IL-10-treated compared to control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats, upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is associated with downregulation of TH1 responses and macrophage function and upregulated TH2 responses.
authors.affiliation: Division of Neurology, Karolinska, Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: X F
authors.initials: XF
authors.lastname: Bai
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: G X
authors.initials: GX
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Kaponides
authors.forename: B
authors.initials: B
authors.lastname: Höjeberg
authors.forename: P H
authors.initials: PH
authors.lastname: van der Meide
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001324:Autoantigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D016753:Interleukin-10 / Q000502:physiology* / Q000627:therapeutic use*; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000517:prevention & control*; D017933:Peripheral Nervous System / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D001324:Autoantigens; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10