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  • Title: Activation of brain macrophages/microglia cells in hepatitis C infection.
    Author: Wilkinson J, Radkowski M, Eschbacher JM, Laskus T.
    Journal: Gut; 2010 Oct; 59(10):1394-400. PubMed ID: 20675697.
    Abstract:
    OBJECTIVES: Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction. Viral sequences and proteins were previously found in brain macrophage/microglia cells. The aim of the current study was to determine whether HCV infection affects the expression of key cytokines and chemokines in these cells. METHODS: Autopsy brain tissue from 15 patients was studied; 7 patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (anti-CD68) and separated by laser capture microscopy. Transcripts representing 25 various cytokines and chemokines were measured by real-time quantitative PCR. RESULTS: Compared with HCV-negative controls, HCV-positive patients demonstrated significantly higher levels of proinflammatory cytokines interleukin 1α (IL-1α), IL-1β, tumour necrosis factor α (TNFα), IL-12 and IL-18. HCV infection was also associated with increased transcription of chemokines IL-8, IL-16 and interferon-inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by increased concentrations of IFNβ and myxovirus resistance protein A (MxA) transcripts. Similar results were obtained when CD68-positive/HCV-positive cells were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected patients. CONCLUSION: Evidence was found for activation of brain macrophages/microglia cells in autopsy brain tissue from HCV-positive patients. These findings could relate to the common presence of neurocognitive dysfunction among patients with chronic hepatitis C.
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