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.

Keywords::

• chemokine
• chemokine receptor
• functional murine model
• human trial
• liver disease
• receptor antagonist

Financial & competing interests disclosure

Work in the laboratory of Hermann E Wasmuth is supported by the Deutsche Forschungsgemeinschaft (SFB TRR57) and Aachen University (IZKF grants). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.