Immune response of Th17-associated cytokines by peripheral blood mononuclear cells from patients with chronic hepatitis C virus infection

• Published in: Cytokine (Philadelphia, Pa.) Vol. 102; pp. 200 - 205
• Main Authors: Cabral, Milena S., Santos, Taciana P.S., Santos, Priscila L., Schinoni, Maria Isabel, Oliveira, Isabela S., Pereira, Ariana B., Atta, Ajax M., Sousa-Atta, Maria Luiza B.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2018
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Antiviral treatment; Autoimmunity; Cytokines - blood; Female; Hepacivirus - immunology; Hepatitis C; Hepatitis C Antigens - immunology; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Humans; Immunity, Cellular; Interferon-alpha - therapeutic use; Interleukin-17 - blood; Interleukin-22; Interleukins - blood; Leukocytes, Mononuclear - immunology; Liver injury; Male; Middle Aged; Protease Inhibitors - therapeutic use; Ribavirin - therapeutic use; Sustained Virologic Response; Th17 Cells - immunology; Th17 cytokines; Autoimmunity; Antiviral treatment; Hepatitis C; Th17 cytokines; Liver injury
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2017.09.015

•Chronic HCV infection caused immune dysregulation.•Th17 cells and their associated cytokines were involved in this process.•HCV core and NS3 antigens induced Th17 immune responses in patients.
Hepatitis C virus (HCV) chronic infection causes severe cellular immune dysfunction. Here, we investigated the production of Th17-associated cytokines by peripheral blood mononuclear cells (PBMCs) of untreated patients with HCV, patients presenting an early virologic response (EVR) after 12weeks of treatment with interferon-α plus ribavirin with or without HCV protease inhibitors, and patients who were nonresponders to HCV therapy. PBMCs were stimulated with HCV core and nonstructural antigens, and the production of Th17-associated cytokines was measured with a Milliplex MAP immunoassay. Core-stimulated PBMCs from both untreated and nonresponder patients produced interleukin (IL)-17A, and vigorous production of IL-17A in response to NS3 antigen was only verified in the untreated group. Nonresponder patients also produced IL-17F after core antigen stimulation. IL-21 production was unaltered in the three groups of patients, whereas IL-17E and IL-22 were not detected. The production of Th17 cytokines by cells from patients showing an EVR was insignificant. IL-17A and IL-17F levels were not correlated with alanine aminotransferase levels or viremia. However, advanced fibrosis was associated with higher IL-17A production in T0 cells stimulated with core antigen. Untreated patients with HCV and patients who were nonresponders to antiviral treatment differed in their PBMC immune responses of Th17-associated cytokines. The early virological response to antiviral treatment dramatically decreased Th17 immune responses to HCV antigens.