Expression of Cytokines (TNF-α, IL-1α, and IL-2) in Chronic Hepatitis C: Comparative Hybridocytochemical and Immunocytochemical Study in Children and Adult Patients

Abstract

Hepatitis C virus (HCV) is one of the principal causes of hepatitis, which in more than 80% of cases leads to chronic lesions in the liver and involvement of extrahepatic organs. It remains unknown why the infection so frequently turns chronic, independently of patient age. Using immunocytochemistry (IHC) and in situ hybridization (ISH) (both linked to the ImmunoMax technique) we examined cell sources of TNF-alpha, IL-1alpha, and IL-2 in control and HCV-infected children and adults. We demonstrated augmented expression of all the cytokines in HCV-infected patients compared to controls. No differences were detected in amounts of studied transcripts or cytokine proteins between biopsies taken from HCV-infected children and adults. Expression of TNF-alpha was localized mainly in liver sinusoidal cells (macrophages, endothelial cells). A high proportion of hepatocytes demonstrated expression of TNF-alpha, IL-1alpha, and IL-2. In both groups of patients, higher amounts of cytokine proteins than studied transcripts were demonstrated. The augmented expression of TNF-alpha, IL-1alpha, and IL-2 in liver with a similar proportion of involved cells (mainly hepatocytes) in children and in adults points to participation of the cytokines in the pathogenesis of chronic hepatitis C. The expression is insufficient to terminate the infection and may be linked with the comparably frequent chronic transformation of HCV infection noted in children and adults.