Chemokines as immune mediators of liver diseases related to the metabolic syndrome.
OBJECTIVE
Chemokines are small chemotactic molecules which regulate the infiltration of immune cells to sites of inflammatory injury. In recent years their contribution to the initiation and perpetuation of liver injury has been better defined. However, the role of chemokines in liver diseases related to the metabolic syndrome still needs to be elucidated in detail.


METHODS
Chemokines were mostly detected at the mRNA level in the liver and as proteins in the serum of patients with non-alcoholic steatohepatitis (NASH) or fatty liver. Animals with targeted deletion of chemokines have recently been subjected to NASH models to functionally dissect the role of chemokines in fatty liver diseases.


RESULTS
In human liver with features of NASH, different CC and CXC chemokines have been detected at elevated mRNA levels in comparison to healthy subjects. Some of these chemokines have also been associated with NASH by demonstrating higher serum levels in affected patients. Until now, only a few animal models have been analyzed with respect to the functional role of these molecules. However, data from CCL2 and CXCR3 knockout mice suggest that these pathways are important in liver injury. CCL2 seems to influence the infiltration of macrophages to adipose tissue and thereby modulate insulin resistance.


CONCLUSIONS
The further elucidation of the pathophysiology of NASH will lead to new therapeutic options to halt or reverse progressive liver disease. In this respect, chemokines are attractive target molecules, as they influence immunologic and metabolic pathways and the first oral chemokine receptor antagonists have already been licensed for humans.
Berres
Marie-Luise
ML
Medical Department III, University Hospital Aachen, RWTH Aachen, Aachen, Germany.
Nellen
Andreas
A
Wasmuth
Hermann E
HE
D000818:Animals; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024821:Metabolic Syndrome / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger