Format

Send to:

Choose Destination
See comment in PubMed Commons below
Gut. 2000 Feb;46(2):260-9.

Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection.

Author information

  • 1The A W Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, Australia.

Abstract

BACKGROUND:

Upregulation of Th1 associated intrahepatic cytokines in chronic hepatitis C virus (HCV) infection should lead to a significant non-specific cellular immune response, a prerequisite for viral clearance. However, to date, the role of this non-specific response in HCV has been understudied.

AIMS:

To analyse the intrahepatic macrophage activity in chronic HCV infection by immunostaining and by quantitation of cytokine mRNA.

METHODS:

HCV positive liver tissues (chronic hepatitis, n=10; cirrhosis, n=5) were immunostained for CD68, MAC387, and semiquantitated by polymerase chain reaction for intrahepatic cytokine mRNAs (interferon gamma (IFNgamma), interleukin 1beta (IL-1beta), IL-6, IL-18, tumour necrosis factor alpha (TNFalpha), and macrophage inflammatory protein 1beta (MIP1beta)). HCV negative normal liver tissues (for cytokines, n=6; for immunostaining, n=5) were included as controls.

RESULTS:

MAC387(+) cells were focally increased in areas of erosion at the limiting plate while lobular staining was minimal. CD68(+) staining was diffuse in both portal (increased in HCV) and lobular areas. The portal tract (mean) density of CD68(+) and MAC387(+) cells was significantly increased in patients with HCV compared with normal tissue. IFNgamma and IL-18 mRNA levels were highly correlated and significantly upregulated in chronic hepatitis and cirrhotic tissue versus controls. TNFalpha mRNA was upregulated in chronic hepatitis without cirrhosis, while IL-6 mRNA was significantly downregulated. IL-1beta, IL-6, and MIP1beta mRNA levels were significantly correlated with portal tract MAC387(+) cell density.

CONCLUSIONS:

The significant upregulation of IFNgamma and IL-18 mRNA and significant correlations between IFNgamma and other proinflammatory cytokines, suggest a Th1/cell mediated intrahepatic immune response in chronic HCV infection. However, further clarification of the cellular sources of these cytokines is required.

PMID:
10644323
[PubMed - indexed for MEDLINE]
PMCID:
PMC1727823
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk