Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis

Authors

  • Olivia M. Martinez,

    1. Transplantation Immunobiology Laboratory, California Pacific Medical Center, San Francisco, CA
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  • Janeth C. Villanueva,

    1. Transplantation Immunobiology Laboratory, California Pacific Medical Center, San Francisco, CA
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  • M. Eric Gershwin,

    1. Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis, CA
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  • Sheri M. Krams PhD

    Corresponding author
    1. Transplantation Immunobiology Laboratory, California Pacific Medical Center, San Francisco, CA
    • California Pacific Medical Center Research Institute, Transplantation Immunobiology Laboratory, 2330 Clay St, Stern Building, San Francisco, CA 94115
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Abstract

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver with unknown etiology. Autoreactive T lymphocytes that infiltrate the liver may play a major role in the bile duct damage that accompanies the disease. We hypothesized that cytokines produced by T lymphocytes and other cells are central to the disease process. Therefore, we used reverse transcription-polymerase chain reaction (PCR) and Southern hybridization to identify cytokine message directly from liver tissue of 11 patients with PBC and 5 patients with autoimmune hepatitis (AI-CAH). Messenger RNA (mRNA) for interleukin (IL)-2, IL-5, IL-6, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β) were detected in the majority of the specimens from patients with PBC. The presence of IL-5 was associated with PBC (P<.001, PBC vs. AI-CAH). Because IL-5 is a potent eosinophil differentiation factor, we looked for evidence of activated eosinophils within the infiltrate. We observed the deposition of the primary cytotoxic granule protein of eosinophils, major basic protein (MBP), within the portal region of livers from patients with PBC. Moreover, we detected message for a cytotoxic T-lymphocyte (CTL) granzyme in 87.5% of these livers indicating that mature CTL are present. Thus, we present evidence for two effector pathways that may contribute to the tissue damage observed in PBC and have identified massage for cytokines that may regulate these pathways. (Hepatology 1995;21:113–119).

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