Chemokines in joint disease: the key to inflammation?

Abstract

Targeting chemokines and/or chemokine receptors appears to be an intriguing new approach to treating chronic inflammatory disorders like rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and transplant rejections. The involvement of chemokines and chemokine receptors in inflammatory joint diseases, the in vitro and in vivo characteristics of the chemokine family in inflammatory joint disease, and initial clinical data on chemokine blockade in patients with rheumatoid arthritis suggest that targeting the chemokine and chemokine receptor family might provide a new, promising antirheumatic strategy.

Figure 1

Overview of homoeostatic and inflammatory functional interactions of chemokines and their receptors in inflammatory joint disease.

Figure 2

Expression of chemokine and chemokine receptor staining in RA ST. CCR1 positive cells are scattered throughout the synovium, and are expressed predominantly by macrophages. There is marked CCR1 expression in the intimal lining layer. CCR2b is expressed by macrophages, especially in the synovial sublining. CCR5 is expressed by both T lymphocytes and macrophages. CXCR4 is mainly expressed by T lymphocytes in the synovial sublining. CCL2/MCP-1, a ligand for CCR2b is almost exclusively expressed in the intimal lining layer. CCL5/RANTES, a ligand for CCR1, CCR3, and CCR5 is expressed in both the intimal lining layer and the synovial sublining. (Single stain peroxidase technique, positive staining in red/brown, Mayer's haematoxylin counterstained, original magnifications x400).