The yin and yang of chemokine receptor activation.

Chemokines represent a class of cytokines that control the migration of leucocytes. The human chemokine system comprises 44 ligands and 21 receptors that have evolved to control leucocyte migration. Although chemokines are an attractive therapeutic target for anti-inflammatory intervention, clinical trials of small molecule receptor antagonists have failed to demonstrate efficacy. One often cited explanation for this is the apparent redundancy within the chemokine system, wherein several ligands bind and activate each receptor. The work of Scholten et al. and Nedjai et al. reported in this issue of the British Journal of Pharmacology demonstrates that this redundancy does not exist at the molecular level and provides a powerful insight into the complex nature of chemokine receptor activation.