title: Improvement of collagen-induced arthritis by active immunization against murine IL-1beta peptides designed by molecular modelling.
abstract: Interleukin-1beta (IL-1beta) is a crucial cytokine in inflammation processes and has been implicated in the pathogenesis of several chronic inflammatory diseases. Strategies designed to blocking IL-1beta by passive administration of inhibitors (mAbs, IL-1 receptor antagonist) have previously demonstrated efficacy in rheumatoid arthritis (RA). Using molecular modelling, we have defined three murine IL-1beta peptide regions characterized by their close proximity to the receptor. Synthetic peptides corresponding to these regions, in cyclic and linear form, were delivered as immunogens in Swiss mice, resulting in significant levels of autoantibodies directed against the native murine IL-1beta cytokine as determined by ELISA and by an assay for neutralization of IL-1beta biological activity. More importantly, one of the cyclic peptides showed a protective effect against inflammation and articular destruction in DBA/1 mouse collagen-induced arthritis, a model of RA. The high rate of success observed for active immunization against cytokine peptides in vivo suggests that the in silico approach to autoantigen design may be a promising avenue for the development of anti-cytokine immunotherapeutics.
authors: Laboratoire d' Oncologie Moléculaire, 2 place Jussieu, Tour 53, 75005 Paris, France.
authors: Sébastien M
authors: SM
authors: Bertin-Maghit
authors: Christelle J
authors: CJ
authors: Capini
authors: Natacha
authors: N
authors: Bessis
authors: Jacques
authors: J
authors: Chomilier
authors: Sylviane
authors: S
authors: Muller
authors: Aïcha
authors: A
authors: Abbas
authors: Ludovic
authors: L
authors: Autin
authors: Jean-Louis
authors: JL
authors: Spadoni
authors: Jay
authors: J
authors: Rappaport
authors: Amu
authors: A
authors: Therwath
authors: Marie-Christophe
authors: MC
authors: Boissier
authors: Jean-François
authors: JF
authors: Zagury
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D003094:Collagen; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000737:chemistry; D007596:Joints / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010455:Peptides; D012795:Sialoglycoproteins; D003094:Collagen