Experimental allergic neuritis: cytolysin mRNA expression is upregulated in lymph node cells during convalescence.
Experimental allergic neuritis (EAN) is a T cell mediated animal model of Guillain-Barré syndrome, characterized by inflammation and demyelination of the peripheral nervous system (PNS). To study the involvement of immunoregulatory cytokines, we induced EAN in Lewis rats by immunizing with bovine PNS myelin (BPM) and Freund's complete adjuvant. mRNA expression of the cytokines IL-1beta, IL-6, IL-10, IL-12, TNF-alpha and TNF-beta, and the cytolytic effector molecule cytolysin was examined in lymph node mononuclear cells (MNC) over the course of EAN by in situ hybridization after culture without antigen and in the presence of BPM, the myelin P2 protein, the control antigen acetylcholine receptor, or the mitogen PHA. Three patterns of cytokine mRNA expressing MNC in relation to clinical EAN could be distinguished: (i) IL-1beta mRNA expressing cells peaked already on day 3 post immunization (p.i.), and BPM- and P2-reactive TNF-alpha, and BPM-reactive IL-6 mRNA expressing cells were also detected already on day 7 p.i., i.e., before onset of clinical EAN; (ii) BPM- and P2-reactive TNF-alpha peaked together with P2-reactive TNF-beta, IL-6 and IL-12 mRNA expressing cells at height of clinical EAN, consistent with a disease-promoting role for these four cytokines; (iii) high levels of BPM- and P2-reactive IL-10 and cytolysin mRNA expressing cells were observed only during recovery (day 28 p.i.), consistent with a disease down-regulating role of IL-10 and cytolysin. The results suggest a major proinflammatory role for IL-1beta, TNF-alpha, TNF-beta, IL-6 and IL-12 and a disease down-regulating function of IL-10 as well as cytolysin in EAN.
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Sweden.
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D000818:Animals; D000941:Antigens / Q000276:immunology; D002417:Cattle; D003289:Convalescence; D003603:Cytotoxins / Q000235:genetics*; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000941:Antigens; D003603:Cytotoxins; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha