title: Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice.
abstract: Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-gamma by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: D J
authors.initials: DJ
authors.lastname: Shuster
authors.forename: K M
authors.initials: KM
authors.lastname: Gillooly
authors.forename: R R
authors.initials: RR
authors.lastname: Warrier
authors.forename: S E
authors.initials: SE
authors.lastname: Connaughton
authors.forename: L B
authors.initials: LB
authors.lastname: Hall
authors.forename: L H
authors.initials: LH
authors.lastname: Arp
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: J
authors.initials: J
authors.lastname: Magram
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology*; D003094:Collagen / Q000276:immunology / Q000633:toxicity*; D007074:Immunoglobulin G / Q000276:immunology; D015994:Incidence; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics / Q000633:toxicity*; D051379:Mice; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains
chemical_list: D007074:Immunoglobulin G; D018664:Interleukin-12; D003094:Collagen