Peripheral Type â…  Interferon Receptor Correlated With Oxidative Stress In Chronic Hepatitis B Virus Infection

Background and ObjectiveIFN-a is the main therapeutic agent for chronic hepatitis B (CHB). It has been effective in suppressing HBV replication and it is a critical mediator of immune response to HBV infection. The effects of type I IFNs are indirect and mediated by interaction with their unique receptors in targeted cell member-type I interferon receptor (IFNAR). IFNAR has been involved in the progression of chronic hepatitis B (CHB). Oxidative stress is also associated with hepatitis B virus (HBV) infection and might contribute to the structure and function of protein synthesis including IFNAR family. This study was aimed to determine the possible associations between oxidative stress and peripheral IFNAR expression in chronic HBV infection in order to discuss the correlation between IFNAR and oxidative stress. Furthermore, the study was aimed to reveal the pathogenesis mechanism of CHB and offer guidance for IFN therapy in the antiviral treatment of CHB.Patients and Methods54CHB patients and31HBV associated decompensated liver cirrhosis (LC) patients were consecutively collected as well as11healthy subjects as controls. Both CHB and LC patients included in this present study were fulfilled the2010chronic hepatitis B practice guideline. Expression of IFNAR1and IFNAR2in peripheral blood lymphocytes and monocytes were measured by flow cytometry (FCM). IFNAR1and IFNAR2c mRNA were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR). Levels of plasma soluble IFNAR and oxidative stress parameters, including xanthine oxidase (XOD), malondialdehyde (MDA), glutathione (GSH). glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) were detected by enzyme linked immunosorbent assay (ELISA).Results1. IFNAR1and IFNAR2expressed in lymphocytes and monocytes were increased in CHB and LC patients compared with healthy controls. Expression of IFNAR1and IFNAR2c mRNA and plasma soluble IFNAR level in CHB and LC patients were up-regulated compared with healthy controls. Mean fluorescence intensity (MFI) of IFNAR2in monocytes of CHB patients was higher than LC patients. Furthermore, percentage of IFNAR2-positve lymphocytes was positively correlated with HBV DNA in serum (log10copies/mL) of CHB patients (r=0.363,p=0.041). MFI of IFNAR1in lymphocytes was negatively correlated with HBV DNA (log10copies/mL) in serum of CHB patients (r=-0.355, p=0.027).2. Levels of plasma XOD, MDA and GST were significantly increased in CHB and LC patients compared with healthy controls. Meanwhile, anti-oxidative parameters of GSH and GSH-Px in CHB and LC patients were decreased. Furthermore, plasma MDA, GSH and GST levels in CHB patients were higher than that in LC patients.3. XOD level was positively correlated with TBIL level (r=0.255, p=0.044) in CHB patients. Meanwhile, in CHB patients, MDA level was positively correlated with ALT level (r=0.41, p=0.001) and GGT level (r=0.488, p<0.001). GSH level was negatively correlated with TBIL level (r=-0.394, p=0.009) in CHB patients. GST level was positively correlated with ALT level (r=0.320,p=0.008) in CHB patients.4. In CHB patients, the level of GST in plasma was negatively correlated with MFI of IFNAR2in lymphocytes (r=-0.447,p=0.01).ConclusionsIFNAR expressed in PBMCs was up-regulated in chronic HBV infection. Oxidative stress was significantly increased in chronic HBV infection patients. The negative correlation IFNAR2in lymphocytes with GST plasma level suggested that oxidative stress played an important role in the regulation of IFNAR in CHB patients.