Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis.

Interleukin-6 (IL-6) plays a key role in the local and systemic manifestations of rheumatoid arthritis (RA). IL-6 is not only a proinflammatory cytokine, but also interacts in complex ways with the cells involved in bone remodeling. In RA, IL-6 may indirectly promote osteoclastogenesis by increasing the release of RANK-L by osteoblasts and synovial cells. However, IL-6 inhibits osteoclastogenesis in vitro, via a direct mechanism. The effects of IL-6 on osteoblasts may vary with the cell differentiation stage: thus, IL-6 may promote the differentiation of pre-osteoblasts to mature osteoblasts while also diminishing the proliferation of osteoblasts at late differentiation stages. Thus, the effects of IL-6 on bone remodeling are complex and may occur in opposite directions depending on the model or experimental conditions. Nevertheless, results from studies in animal models and humans support a negative effect of IL-6 on bone. Thus, in patients with RA, blocking IL-6 may be effective both in diminishing the inflammatory manifestations and in preventing the bone complications of the disease. Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.