AN ANTIINFLAMMATORY ROLE FOR INTERLEUKIN-11 IN ESTABLISHED MURINE COLLAGEN-INDUCED ARTHRITIS

Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family whic h has both pro- and antiinflammatory potential. Like IL-6 it can dimin ish tumour necrosis factor-alpha and IL-1 production, and augment immu noglobulin synthesis. We have explored the immunomodulatory effects of IL-11 treatment in mice in a model of inflammatory autoimmune joint d isease, 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 da mage, as assessed by histology. Although there was a suggestion at hig h doses of IL-11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL-1 1 treatment on anti-CII antibody levels. Similarly, the acute-phase re actant serum amyloid P was only elevated in mice receiving very high d oses (50-100 mu g/day) of IL-11. Endogenous IL-11 was abundantly produ ced in synovial membrane cultures derived from CII-immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cyt okine is spontaneously produced in the inflammatory response in CIA. T he results presented here demonstrate an anti-arthritic immunoregulato ry role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.