Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB)


Dr E. A. Jones Chief of Hepatology, Department of Gastrointestinal and Liver Diseases, Room C2-330, Academ. Ziekenhuis bij de Universteit van Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.


The expression of cytokine mRNA species was determined in liver biopsies from six normal subjects, 18 patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by reverse transcription using oligo d(T) primers, was amplified by PCR using primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α)). The abundance of some cytokines (IL-2, IL-4, IL-5 and IFN-γ) was also estimated by semiquantitative RT-PCR, using as standards dilutions of synthetic cytokine mRNA transcripts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquantitative histologic score and by amplification of mRNA for T cell receptor (TCR)-α. mRNAs for IL-1 and IL-6 were detected in only one control liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-γ were detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-γ and IL-4, but not IL-1, tended to be associated with severe inflammation. In five biopsies semiquantitative analyses revealed increased levels of mRNA for TCR-α and, when transcripts were detectable, high levels of mRNA for IFN-γ and IL-4. In PBC, mRNA for IFN-γ was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-α, were detected. Semiquantitative analyses revealed that absolute levels of mRNA for IFN-γ tended to correlate with the severity of hepatic inflammation. The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-γ mRNA expression is not specific for PBC, IFN-γ may play a prominent role in the immunopathogenesis of PBC.