title: Soluble recombinant complement receptor 1 inhibits inflammation and demyelination in antibody-mediated demyelinating experimental allergic encephalomyelitis.
abstract: Activation of complement may contribute to tissue damage in many inflammatory diseases, including those that are clearly T cell driven. We have previously provided evidence that C is involved in tissue damage in multiple sclerosis and in the animal models of this disease, experimental allergic encephalomyelitis and Ab-mediated demyelinating experimental allergic encephalomyelitis, the latter being a model more closely resembling multiple sclerosis. The development of a soluble recombinant form of human complement receptor 1 (sCR1) with potent C-inhibiting activity both in vitro and in vivo provides a potential means of preventing C-mediated tissue damage in animal models and in human disease. Here, we describe the effects of this agent on clinical disease and pathology in Ab-mediated demyelinating experimental allergic encephalomyelitis in the rat. Daily i.p. injection of sCR1 (20 mg/kg) over 6 days completely suppressed serum C activity, reduced the severity of clinical disease (clinical score 1.33 vs 2.79 in untreated animals), inhibited central nervous system inflammation (inflammatory index 2.76 vs 6.55), and almost completely blocked demyelination (average 2.43% cord cross-section vs 8.81%). Deposition of C components C1, C3, and C9 was also markedly inhibited in sCR1-treated animals. This dramatic effect on a demyelinating disease, achieved using a well-tolerated biologic reagent, offers an exciting new prospect for therapy in multiple sclerosis.
authors.affiliation: Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Piddlesden
authors.forename: M K
authors.initials: MK
authors.lastname: Storch
authors.forename: M
authors.initials: M
authors.lastname: Hibbs
authors.forename: A M
authors.initials: AM
authors.lastname: Freeman
authors.forename: H
authors.initials: H
authors.lastname: Lassmann
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017463:Receptors, Complement 3b / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins