Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C.
BACKGROUND
The mechanisms leading to hepatic injury in chronic hepatitis C virus (HCV) infection are only incompletely understood. Recent data propose a correlation of the intrahepatic expression of the CC chemokine RANTES and the degree of periportal and portal inflammatory liver damage.


OBJECTIVE
Here, we have studied the intrahepatic mRNA levels of CC chemokines RANTES together with that of other members of this chemokine family (MIP-1beta, MCP-1, and MCP-2) in chronic hepatitis C as compared with healthy controls.


METHODS
Liver samples from 22 HCV-infected patients, nine individuals with primary biliary cirrhosis and from 12 normal controls were included into this study. Intrahepatic mRNA levels of CC chemokines RANTES, MIP-1beta, MCP-1, and MCP-2 were analyzed by a semi-quantitative reverse transcription/real-time polymerase chain reaction assay.


RESULTS
In chronic HCV infection, intrahepatic RANTES mRNA levels were significantly higher than in non-infected controls (7.2-fold, p < 0.001) or in the disease control group (2.8-fold, p < 0.001) and higher levels of RANTES mRNA levels were observed in livers with an advanced stage of liver cell injury (histologic activity index > or = 6), although this difference was not statistically significant (p = 0.08). In contrast, mRNA levels of MIP-1beta (p = 0.021) and MCP-1 (p = 0.021) were significantly lower in HCV liver samples while MCP-2 expression was similar in all groups analyzed.


CONCLUSIONS
The data support the concept of chemokines as mediators of liver cell injury in chronic hepatitis C.
Nischalke
Hans Dieter
HD
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Nattermann
Jacob
J
Fischer
Hans-Peter
HP
Sauerbruch
Tilman
T
Spengler
Ulrich
U
Dumoulin
Franz Ludwig
FL
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics; D054412:Chemokine CCL8; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000235:genetics / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C111835:CCL2 protein, human; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054412:Chemokine CCL8; D019742:Chemokines, CC; D018836:Inflammation Mediators; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger