Involvement of the Interleukin-23/Interleukin-17 Axis in Chronic Hepatitis C Virus Infection and Its Treatment Responses

Abstract

Interleukin-23 (IL-23) and its downstream factor IL-17 are the key cytokines involved in immune and inflammatory response in chronic liver diseases. This study aimed to investigate the role and molecular mechanisms of the IL-23/Th17 axis in chronic hepatitis C virus (HCV) infection, and the efficacy of IL-23/Th17 modulation in response to anti-HCV therapy. Sixty-six HCV-infected patients and 20 healthy controls were enrolled. The patients received PegIFNa-2a and ribavirin therapy for at least 48 weeks. The plasma level of IL-23 and the number of IL-17A-, IFN-γ-, and IL-21-producing peripheral blood mononuclear cells (PBMCs) at baseline and 12, 24, and 48 weeks following treatment were determined. The mRNA level of Th17 immune-associated molecules in PBMCs was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) following treatment with IL-23 agonist or antagonist. Our data showed that, compared to healthy controls, HCV-infected patients had an increased plasma level of IL-23 and increased frequencies of IL-17A- and IFN-γ-producing PBMCs, whereas the HCV patients exhibited a reduced number of IL-21-producing PBMCs. However, the baseline frequencies of IL-21-producing PBMCs were markedly higher in HCV patients who achieved rapid virological response (RVR) than those without RVR. Additionally, the mRNA expressions of IL-21, IFN-γ, myxovirus resistance protein A (MxA), and suppressor of cytokine signaling 3 (SOCS3) were significantly upregulated in PBMCs, while FoxP3 expression was suppressed by IL-23 agonist. Thus, the IL-23/Th17 axis plays an important role in development of chronic HCV infection and antiviral response. IL-23 may enhance the antiviral activity of interferon-based therapy by modulating the expression of Th17 cells-associated molecules in HCV-infected patients.

Levels of Interleukin-17 and Vitamin D and Their Correlation in Viral Hepatitis Patients

“…[14] The differences between the means of the patients and control groups (Z = -2.139) were significant at (p<0.05) which is most likely due to the important role that IL 17 plays during the chronic viral infection in indicating liver damage as explained previously in the literature review chapter. [12] Results also showed a highly significant decrease (P <0.01) in trimmed mean of IL-17 serum levels in HBV patients when compared to HCV patients group (Z = -4.321). In agreement, Sousa [15] found the mean of IL-17 serum level in HCV patients to be (96.8ng/L) while Du [16] found the mean of Il-17 in HBV patients to be (38.9 ng/L), which is lower than in HCV cases.…”

“…It was also suggested that antiviral treatment lowers the levels of IL-17 in patients' serum. [12] , [13] This decrease in IL-17 seems to favor the survival of subjects under treatment. [14] The differences between the means of the patients and control groups (Z = -2.139) were significant at (p<0.05) which is most likely due to the important role that IL 17 plays during the chronic viral infection in indicating liver damage as explained previously in the literature review chapter.…”

Intrahepatic TH17/TReg Cells in Homeostasis and Disease—It’s All About the Balance

“…In contrast, virus-specific T H 17 cells were correlated with liver injury and inflammation, but T H 17 quantity could not be linked to effective viral clearance. Furthermore, IL-23 and IL-17 levels in HCV-infected patients were elevated, and IL-23 therapy was reported to modulate the antiviral response by preferentially promoting T H 17 immune cells ( Meng et al, 2016 ). In a course of HCV infection, T Reg cells were mainly found in necro-inflammatory liver areas to inhibit the effector CD8 T cell response, which is the main cause of liver damage in HCV and hepatitis B virus (HBV) infection.…”

A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

“…Alteration in the interleukin-23 (IL-23)/Th17 signaling axis has been suggested as an important trigger for chronic inflammation [66,67,68,69,70,71,72]. Briefly, this pathway corresponds to the polarization of naïve CD4 positive cells towards a T-helper cell (Th17) phenotype, associated with by the predominant production of IL-17 and IL-22.…”