An anti-inflammatory role for interleukin-11 in established murine collagen-induced arthritis.
Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family which has both pro- and anti-inflammatory potential. Like IL-6 it can diminish tumour necrosis factor-alpha and IL-1 production, and augment immunoglobulin synthesis. We have explored the immunomodulatory effects of IL-11 treatment in mice in a model of inflammatory autoimmune joint disease, collagen-induced arthritis (CIA). Recombinant human IL-11 was administered at various doses to DBA/1 mice after the onset of CIA. IL-11 treatment caused a significant reduction in the clinical severity of established CIA, which was associated with protection from joint damage, as assessed by histology. Although there was a suggestion at high doses of IL-11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL-11 treatment on anti-CII antibody levels. Similarly, the acute-phase reactant serum amyloid P was only elevated in mice receiving very high doses (50-100 microgram/day) of IL-11. Endogenous IL-11 was abundantly produced in synovial membrane cultures derived from CII-immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cytokine is spontaneously produced in the inflammatory response in CIA. The results presented here demonstrate an anti-arthritic immunoregulatory role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.
Kennedy Institute of Rheumatology, London, UK.
M
M
Walmsley
D M
DM
Butler
L
L
Marinova-Mutafchieva
M
M
Feldmann
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006614:Hindlimb; D007074:Immunoglobulin G / Q000032:analysis; D016753:Interleukin-10 / Q000627:therapeutic use; D017370:Interleukin-11 / Q000627:therapeutic use*; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000627:therapeutic use; D000685:Serum Amyloid A Protein / Q000032:analysis
D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D017370:Interleukin-11; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D016753:Interleukin-10; D003094:Collagen