CYTOKINE MESSENGER-RNA EXPRESSION IN THE LIVER OF PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS (PBC) AND CHRONIC HEPATITIS-B (CHB)

The expression of cytokine mRNA species was determined in liver biopsi es from six normal subjects, Is patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcript ase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by re verse transcription using oligo d(T) primers, was amplified by PCR usi ng primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), tumour n ecrosis factor-alpha (TNF-alpha)). The abundance of some cytokines (IL -2, IL-4, IL-5 and IFN-gamma) was also estimated by semiquantitative R T-PCR, using as standards dilutions of synthetic cytokine mRNA transcr ipts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquan titative histologic score and by amplification of mRNA for T cell rece ptor (TCR)-alpha. mRNAs for IL-1 and IL-6 were detected in only one co ntrol liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-gamma we re detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-gamma and IL-4, but not IL-1, tended to be associated wit h severe inflammation. In five biopsies semiquantitative analyses reve aled increased levels of mRNA for TCR-alpha and, when transcripts were detectable, high levels of mRNA for IFN-gamma and IL-4. In PBC, mRNA for IFN-gamma was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-alpha, were detected. Semiquanti tative analyses revealed that absolute levels of mRNA for IFN-gamma te nded to correlate with the severity of hepatic inflammation. The resul ts 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-gamma mRNA expression is not specific for PBC, IFN-gamma may play a prominent role in the immunopathogenesis of PBC.