New dimensions in our understanding of immune cell trafficking have been opened by the discovery of chemokines and their receptors. This family of chemo-attractant cytokines shares a high degree of structural homology, performing essential roles in the recruitment and subsequent positioning of leucocyte subsets within tissue microenvironments. Diverse roles have been demonstrated in inflammation, tumorigenesis and haematopoiesis, in addition to crucial roles in tissue and lymphoid development. Investigation of chemokine networks offers a novel approach to many of the poorly understood mysteries of persistent inflammatory diseases such as rheumatoid arthritis, where evidence is mounting that the inappropriate temporal and spatial expression of chemokines and / or their receptors may impair the resolution of leucocyte infiltrates, thereby giving rise to persistent inflammation. However, while they offer ready targets for pharmacological intervention, the complexity of chemokine / chemokine receptor interactions renders their therapeutic manipulation in clinical practice challenging. We review the structure and function of chemokines and their receptors, and discuss the problems involved in potential therapeutic applications. We then review the most recent data on therapeutic applications of molecules interacting with the chemokine system with specific reference to rheumatoid arthritis.
Keywords: chemokine, chemokine receptor, antagonist, rheumatoid arthritis, inflammation, fibroblast, microenvironment
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