Chemokines and Receptors as Targets in Anti-Inflammatory Therapy

An essential feature of different inflammatory conditions, such as infective, autoimmune, allergic or vascular diseases, is the recruitment of infiltrating leukocytes. A large number of chemoattractant cytokines termed chemokines appear as critical factors in the development of inflammatory cell infiltration by interacting with specific receptors on leukocytes and regulating leukocyte movements. Chemokines may also play important roles in many other leukocyte functions such as differentiation of effector phenotypes or cell growth.A limitation to understand the participation of chemokines in chronic inflammatory diseases and to the development of chemokine based therapy is redundancy and overlapping receptor-ligand profiles of this system. However, emerging evidences point to specific roles for individual chemokines or chemokine receptors in many chronic inflammatory disorders such as glomerulonephritis, multiple sclerosis, rheumatoid arthritis, atherosclerosis and lung and airway inflammatory diseases. Genetic deletion of chemokines or their receptors have confirmed a relevant role for these factors in murine models of inflammation.A variety of common drugs used to treat human inflammatory disease, including those inhibiting NF-κB activation, have indirect effects on chemokines expression. More potent and specific strategies for inhibition of different chemokines or their receptors are being developed. Neutralizing antibodies or a variety of peptides or small molecules have demonstrated their potential to target leukocyte infiltration in different animal models and provide the basis for their use to treat human inflammatory diseases.