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.
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-infectedpatients. 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.
Authors: Jennifer M Loftis; Juno Valerio; Jonathan Taylor; Elaine Huang; Rebekah Hudson; Patricia Taylor-Young; Michael Chang; Samuel B Ho; Eric Dieperink; Juan Luis Miranda; Peter Hauser Journal: Alcohol Clin Exp Res Date: 2018-06-28 Impact factor: 3.455
Authors: David A Sheridan; S H Bridge; M M E Crossey; D J Felmlee; H C Thomas; R D G Neely; S D Taylor-Robinson; M F Bassendine Journal: Metab Brain Dis Date: 2014-03-12 Impact factor: 3.584
Authors: Christopher Power; Elizabeth Hui; Pornpun Vivithanaporn; Shaona Acharjee; Maria Polyak Journal: J Neuroimmune Pharmacol Date: 2011-09-15 Impact factor: 4.147