Nowell, Mari Ann, Richards, Peter James, Horiuchi, Sankichi, Yamamoto, Naoki, Rose-John, Stefan, Topley, Nicholas, Williams, Anwen Sian ![]() ![]() |
Abstract
Studies in IL-6-deficient (IL-6-/-) mice highlight that IL-6 contributes to arthritis progression. However, the molecular mechanism controlling its activity in vivo remains unclear. Using an experimental arthritis model in IL-6-/- mice, we have established a critical role for the soluble IL-6R in joint inflammation. Although intra-articular administration of IL-6 itself was insufficient to reconstitute arthritis within these mice, a soluble IL-6R-IL-6 fusion protein (HYPER-IL-6) restored disease activity. Histopathological assessment of joint sections demonstrated that HYPER-IL-6 increased arthritis severity and controlled intrasynovial mononuclear leukocyte recruitment through the CC-chemokine CCL2. Activation of synovial fibroblasts by soluble IL-6R and IL-6 emphasized that these cells may represent the source of CCL2 in vivo. Specific blockade of soluble IL-6R signaling in wild-type mice using soluble gp130 ameliorated disease. Consequently, soluble IL-6R-mediated signaling represents a promising therapeutic target for the treatment of rheumatoid arthritis.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences Medicine Systems Immunity Research Institute (SIURI) |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
Last Modified: | 05 Feb 2025 22:34 |
URI: | https://orca.cardiff.ac.uk/id/eprint/286 |
Citation Data
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