title: Interleukin-1 receptor antagonist suppresses experimental autoimmune encephalomyelitis (EAE) in rats by influencing the activation and proliferation of encephalitogenic cells.
abstract: Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although the role of CD4+ T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated, the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. We have evaluated the effect of human recombinant interleukin-1 receptor antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 microg/rat/day) developed milder signs of EAE, when compared to saline-treated control animals immunized with encephalitogen, which developed severe single episode disease. The transfer of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 microg/ml) developed significantly milder disease. Diminished encephalitogenic capacity of LNC correlated with lower proliferative response to antigen and mitogen and decreased expression of IL-2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lymphocytes.
authors.affiliation: Institute for Biological Research Sinisa Stanković, University of Belgrade, Yugoslavia.
authors.forename: V
authors.initials: V
authors.lastname: Badovinac
authors.forename: M
authors.initials: M
authors.lastname: Mostarica-Stojković
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: S
authors.initials: S
authors.lastname: Stosić-Grujicić
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004676:Myelin Basic Protein / Q000494:pharmacology; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins
chemical_list: D004676:Myelin Basic Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D003208:Concanavalin A