Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice.
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.
McIntyre
K W
KW
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Shuster
D J
DJ
Gillooly
K M
KM
Warrier
R R
RR
Connaughton
S E
SE
Hall
L B
LB
Arp
L H
LH
Gately
M K
MK
Magram
J
J
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
D007074:Immunoglobulin G; D018664:Interleukin-12; D003094:Collagen