Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis.
Interleukin-6 (IL-6) is highly produced during arthritis but its exact function is still unknown. In this study we examined if IL-6, apart from its role in immunity, was involved in the local inflammatory response in experimental arthritis. IL-6 deficient (IL-6(-/-)) and wild-type mice were first compared in the antigen-induced arthritis model. IL-6 deficiency resulted in a mild, transient inflammation whereas wild-type mice developed a chronic, destructive synovitis. Wild-type mice immunized with one-tenth of the normal antigen dose still developed chronic arthritis despite low antibody levels, excluding reduced humoral immunity in IL-6(-/-) mice as a crucial phenomenon. In addition, passive immune-complex-induced arthritis did not differ between wild-type and IL-6(-/-) mice. Another option is reduced levels of Th1 cells in IL-6(-/-) mice. However, transfer of antigen-specific wild-type lymph node cells to IL-6(-/-) mice enhanced acute joint inflammation and increased cartilage damage but still could not sustain chronic inflammation, suggesting involvement of nonimmune elements of IL-6 activity in chronicity. In line with this, nonimmunologically mediated zymosan-induced arthritis developed similarly in the first week, but only wild-type mice developed chronic synovitis. These results indicate an important role for IL-6 in propagation of joint inflammation, potentially independent of its role in immunity.
de Hooge
A S
AS
Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands. A.deHooge@reuma.azn.nl
van De Loo
F A
FA
Arntz
O J
OJ
van Den Berg
W B
WB
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D017690:Cell Transplantation; D018925:Chemokines / Q000378:metabolism; D003167:Complement Activation; D000939:Epitopes; D007109:Immunity / Q000502:physiology*; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015054:Zymosan
D000906:Antibodies; D015815:Cell Adhesion Molecules; D018925:Chemokines; D000939:Epitopes; D015850:Interleukin-6; D012710:Serum Albumin, Bovine; D015054:Zymosan