Collagen-induced arthritis is exacerbated in IL-10-deficient mice.
IL-10 is a potent immunoregulatory cytokine attenuating a wide range of immune effector and inflammatory responses. In the present study, we assess whether endogenous levels of IL-10 function to regulate the incidence and severity of collagen-induced arthritis. DBA/1 wildtype (WT), heterozygous (IL-10+/-) and homozygous (IL-10-/-) IL-10-deficient mice were immunized with type II collagen. Development of arthritis was monitored over time, and collagen-specific cytokine production and anticollagen antibodies were assessed. Arthritis developed progressively in mice immunized with collagen, and 100% of the WT, IL-10+/-, and IL-10-/- mice were arthritic at 35 days. However, the severity of arthritis in the IL-10-/- mice was significantly greater than that in WT or IL-1+/- animals. Disease severity was associated with reduced IFN-gamma levels and a dramatic increase in CD11b-positive macrophages. Paradoxically, both the IgG1 and IgG2a anticollagen antibody responses were also significantly reduced. These data demonstrate that IL-10 is capable of controlling disease severity through a mechanism that involves IFN-gamma. Since IL-10 levels are elevated in rheumatoid arthritis synovial fluid, these findings may have relevance to rheumatoid arthritis.
Finnegan
Alison
A
Department of Medicine, Section of Rheumatology, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois, USA. Alison_Finnegan@rush.edu
Kaplan
Charles D
CD
Cao
Yanxia
Y
Eibel
Hermann
H
Glant
Tibor T
TT
Zhang
Jian
J
D000818:Animals; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D039481:CD11b Antigen / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology; D018450:Disease Progression; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology
D039481:CD11b Antigen; D016753:Interleukin-10; D007371:Interferon-gamma; D003094:Collagen