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

PH McGuinness, D Painter, S Davies, GW McCaughan - Gut, 2000 - gut.bmj.com
PH McGuinness, D Painter, S Davies, GW McCaughan
Gut, 2000gut.bmj.com
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 …
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 γ (IFNγ), interleukin 1β (IL-1β), IL-6, IL-18, tumour necrosis factor α (TNFα), and macrophage inflammatory protein 1β (MIP1β)). 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. IFNγ and IL-18 mRNA levels were highly correlated and significantly upregulated in chronic hepatitis and cirrhotic tissue versus controls. TNFα mRNA was upregulated in chronic hepatitis without cirrhosis, while IL-6 mRNA was significantly downregulated. IL-1β, IL-6, and MIP1β mRNA levels were significantly correlated with portal tract MAC387+ cell density.
CONCLUSIONS
The significant upregulation of IFNγ and IL-18 mRNA and significant correlations between IFNγ 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.
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