LAUSR

Chemokines, a family of small secreted chemotactic cytokines, and their G protein-coupled seven transmembrane spanning receptors control the migratory patterns, positioning and cellular interactions of immune cells. The levels of chemokines and their receptors are increased in the blood and within inflamed tissue of patients with rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis or idiopathic inflammatory myopathies. Chemokine ligand–receptor interactions control the recruitment of leukocytes into tissue, which are central to the pathogenesis of these rheumatic diseases. Although the blockade of various chemokines and chemokine receptors has yielded promising results in preclinical animal models of rheumatic diseases, human clinical trials have, in general, been disappointing. However, there have been glimmers of hope from several early-phase clinical trials that suggest that sufficiently blocking the relevant chemokine pathway might in fact have clinical benefits in rheumatic diseases. Hence, the chemokine system remains a promising therapeutic target for rheumatic diseases and requires further study.Chemokines have an important function in the recruitment and positioning of immune cells, and multiple chemokines are implicated in various rheumatic diseases. Blocking the chemokine system has therapeutic promise for the treatment of these diseases but requires further optimization.Key pointsChemokines are a large family of secreted chemotactic cytokines that control the recruitment of immune cells into tissue and their cellular interactions once in tissue.Chemokine receptors are G protein-coupled seven transmembrane spanning proteins that are expressed on immune cells and regulate their migration and cell–cell interactions.Concentrations of chemokines are increased in the blood and tissues of patients with rheumatic diseases, suggesting their involvement in the pathogenesis of these diseases and highlighting them as therapeutic targets.Preclinical animal models of rheumatic diseases show the important functional roles of the chemokine system in the pathogenesis of these diseases.Unfortunately, the majority of clinical trials testing the efficacy of chemokine and chemokine receptor inhibitors have failed to show meaningful clinical benefit.However, several clinical studies have shown promise and suggest that targeting the relevant chemokine system and ensuring complete inhibition at all times might be needed for therapeutic benefit.