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

M. Shindo, G. E. Mullin, L. Braun-Elwert, N. V. Bergasa, E. A. Jones, S. P. James

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)254-259
Number of pages6
JournalClinical and Experimental Immunology
Volume105
Issue number2
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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Keywords

  • Cytokines
  • Hepatitis B
  • Liver biopsy
  • Primary biliary cirrhosis
  • mRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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