Tomasz Pawlowski1, Marek Radkowski2, Krzysztof Małyszczak1, Małgorzata Inglot3, Małgorzata Zalewska3, Joanna Jablonska4, Tomasz Laskus5. 1. Division of Psychotherapy and Psychosomatic Medicine, Wrocław Medical University, Wrocław, Poland. 2. Department of Immunopathology, Medical University of Warsaw, Warsaw, Poland. 3. Department of Infectious Diseases, Hepatology and Acquired Immune Deficiencies, Wrocław Medical University, Wrocław, Poland. 4. Department of Hepatology and Acquired Immunodeficiency Syndrome, Medical University of Warsaw, Warsaw, Poland. 5. Department of Immunopathology, Medical University of Warsaw, Warsaw, Poland. Electronic address: tlaskus@yahoo.com.
Abstract
BACKGROUND: Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction and depression, which could be related to direct brain infection. Viral sequences and proteins were found in brain macrophage/microglia cells and these cells were reported to be activated. Since blood leukocytes cross blood-brain barrier, activation state of peripheral blood mononuclear cells (PBMC) could reflect the state of brain immune cells. OBJECTIVE: The aim of the study was to determine whether depression and neuroticism in chronic HCV infection correlates with the expression of key cytokines and chemokines in PBMC. DESIGN: We studied 24 HCV-positive patients undergoing treatment with interferon and ribavirin. Patients were tested for depression using Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS), while neuroticism was assessed by the Revised Eysenck Personality Inventory (N/EPO-R). Transcripts representing 28 various cytokines and chemokines were measured by real-time quantitative PCR in PBMC. RESULTS: Prior to therapy BDI and MADRS positively correlated with viral load while neuroticism correlated with IL-3, IL-8 and M-CSF transcription levels. Six months after therapy there was positive correlation between depression and/or neuroticism scores and the levels of proinflammatory cytokines TNF-α and IL-12 transcripts, as well as IL-8, IL-10, IL-16, MCP-1, MCP-2, MIP-1-alpha, MIP-1-beta, and TGF-beta, and IFN-β transcripts. CONCLUSION: Activation of PBMC, as measured by the level of cytokine and chemokine transcripts, correlates with depression and neuroticism scores. These findings suggest a pivotal role of immune cells activation in depression and possibly neurocognitive dysfunction among chronic hepatitis C patients.
BACKGROUND:Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction and depression, which could be related to direct brain infection. Viral sequences and proteins were found in brain macrophage/microglia cells and these cells were reported to be activated. Since blood leukocytes cross blood-brain barrier, activation state of peripheral blood mononuclear cells (PBMC) could reflect the state of brain immune cells. OBJECTIVE: The aim of the study was to determine whether depression and neuroticism in chronic HCV infection correlates with the expression of key cytokines and chemokines in PBMC. DESIGN: We studied 24 HCV-positive patients undergoing treatment with interferon and ribavirin. Patients were tested for depression using Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS), while neuroticism was assessed by the Revised Eysenck Personality Inventory (N/EPO-R). Transcripts representing 28 various cytokines and chemokines were measured by real-time quantitative PCR in PBMC. RESULTS: Prior to therapy BDI and MADRS positively correlated with viral load while neuroticism correlated with IL-3, IL-8 and M-CSF transcription levels. Six months after therapy there was positive correlation between depression and/or neuroticism scores and the levels of proinflammatory cytokines TNF-α and IL-12 transcripts, as well as IL-8, IL-10, IL-16, MCP-1, MCP-2, MIP-1-alpha, MIP-1-beta, and TGF-beta, and IFN-β transcripts. CONCLUSION: Activation of PBMC, as measured by the level of cytokine and chemokine transcripts, correlates with depression and neuroticism scores. These findings suggest a pivotal role of immune cells activation in depression and possibly neurocognitive dysfunction among chronic hepatitis Cpatients.
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