Therapeutic potential of chemokine receptor antagonists for liver disease

Abstract

Chemokines are a family of small heparin-binding proteins that orchestrate the infiltration of immune cells into the liver, but also directly influence the biology of resident liver cells. A nonredundant role of different chemokines and their receptors has been identified within the last years in animal models of acute and chronic liver diseases. Chemokine receptors that have been shown to play an import pathophysiological role in the liver are CCR1, CCR2, CCR5, D6, CXCR2 and CXCR3. Interestingly, most of these receptors have already been targeted by specific antagonists in early human trials and a CCR5 antagonist is already licensed for use in HIV infection. Most of these trials have been performed in autoimmune and infectious human diseases, but no controlled clinical trials have yet been performed in patients with liver diseases. Nevertheless, in light of growing evidence that chemokines are important mediators of liver damage, these trials seem to be on the clinical horizon.