Serum Levels of IL-6, IL-8, TNF-α, and TGF-ß in Chronic HBV-Infected Patients: Effect of Depression and Anxiety.

OBJECTIVE: To assess the effects of depression and anxiety on serum cytokine levels in patients with chronic hepatitis B (CHB) infection. METHODS: In this cross-sectional study, 60 healthy control individuals and 60 patients with CHB participated after filling out standard questionnaires. We examined their serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and TGF-ß levels using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: In patients with CHB compared with healthy controls, serum levels of IL-8 were significantly increased, whereas IL-6 and TGF-ß levels were significantly decreased. Serum levels of TGF-ß were significantly decreased in the patients with CHB who had mild depression, compared with patients with CHB without depression and with moderate and severe depression. CONCLUSIONS: Downregulation of IL-8 and TGF-ß, respectively, is a corresponding mechanism for induction of chronic inflammation in patients with CHB. Depression also seems to induce inflammation via downregulation of TGF-ß in these patients.

Evaluation of NLRC4, NLRP1, and NLRP3, as Components of Inflammasomes, in Chronic Hepatitis B Virus-Infected Patients.

Nucleotide-binding domain leucine repeats (NLRs) are required for the recognition of various molecules that are expressed within microbes and are able to actuate appropriate immune responses via activation of cytokines. The current study evaluates the expression levels of NLRP1 and NLRC4, which are components of inflammasomes, in chronic hepatitis B (CHB) virus-infected patients. This study recruited two series of CHB patients (each contained 60 patients) and 60 healthy controls. Real-time polymerase chain reaction (PCR) was employed to evaluate mRNA expression levels of NLRP1, NLRP3, and NLRC4 as well as hepatitis B virus (HBV)-DNA copy number. Serum levels of liver markers were also used to evaluate the patients. Hepatitis B envelope antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were also examined in all patients to evaluate infection. The data showed that expression levels of NLRC4 and NLRP1 were not significantly different in circulating monocytes of CHB patients when compared with those of healthy controls. Furthermore, the data indicate that mRNA levels of NLRP1, NLRP3, and NLRC4 were also not altered in CHB patients regardless of HBV-DNA copy numbers/mL and HBeAg status. The data revealed that mRNA expression levels of NLRP1 and NLRC4 were not altered in CHB patients, suggesting that these genes are not responsible for the impaired immune responses against HBV observed in these patients.

Are RIG-1 and MDA5 Expressions Associated with Chronic HBV Infection?

Melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) as the pattern recognition receptors play important roles in viral mRNA recognition. Chronic HBV-infected (CHB) patients are unable to properly respond to hepatitis B virus (HBV). Therefore, the aim of the present study was to evaluate the mRNA levels of MDA5 and RIG-1 in the peripheral blood immune cells of CHB patients in comparison to healthy controls. In this cross-sectional study, the mRNA levels of MDA5 and RIG-1 were examined in 60 CHB patients and 60 healthy controls using the real-time polymerase chain reaction (PCR) technique. Our results showed that mRNA levels of MDA5 and RIG-1 were significantly decreased and increased, respectively, in CHB patients when compared to healthy controls. Our results also revealed that mRNA levels of MDA5 and RIG-1 were not altered among CHB patients with various states of e-antigen of hepatitis B and HBV-DNA viral loads. According to the results presented here, it may be concluded that downregulation of MDA5 may be a responsible mechanism from several reasons, which leads to HBV persistence in CHB patients.

The effect of depression and anxiety on expression levels of toll like receptor signaling molecules in chronic HBV infected patients.

BACKGROUND: Toll- like receptors (TLRs) play an important role in the recognition of DAMPs and PAMPs and induction of inflammation. Previous studies demonstrated that depression and anxiety can influence the expression levels of immune related molecules. Our previous study revealed that mRNA levels of IRAKIRAK4, TRAF3 and IRF7 were significantly decreased in chronic HBV infected (CHB) patients when compared to healthy controls. Therefore, the aim of this study was to evaluate the effects of depression and anxiety on the expression levels of these molecules in CHB patients. METHODS: Sixty CHB patients participated in this study and filled out the standard questionnaires; and the expression of IRAK4, TRAF3 and IRF7 were examined using Real-Time PCR techniques. RESULTS: The results of this study demonstrated that expression of IRAK4, TRAF3 and IRF7 did not differ between patients with various stages of depression and anxiety (all p>0.05). CONCLUSION: According to the results, it seems that declined expression of IRAK4, TRAF3 and IRF7 in CHB patients were not related to depression and anxiety, and other factors including genetic and immunoregulatory effects of HBV may be responsible for the declined expression of these molecules.

Decreased Expressions of STING but not IRF3 Molecules in Chronic HBV Infected Patients.

CONTEXT: The stimulator of interferon genes (STING) induces the activation of interferon regulatory factor 3 (IRF3) in response to intracellular viral double-stranded (ds) DNA. The aim of this study was to evaluate mRNA levels of STING and its downstream transcription factor, IRF3, in the isolated peripheral blood mononuclear cells (PBMCs) of patients with chronic HBV (CHB) infection. METHODS: This study was performed on 60 healthy controls and 60 CHB patients. The mRNA levels of STING and IRF3 were determined using Real-Time polymerase chain reaction (PCR) techniques. The SPSS software version 18 was used to analyze raw data. RESULTS: The results revealed that mRNA levels of STING were significantly decreased in CHB patients in comparison to healthy controls (P = 0.013). Our results also revealed that expression levels of IRF3 were not different between CHB patients and healthy controls (P = 0.828). CONCLUSIONS: In the present study, we found that CHB patients were unable to express appropriate levels of STING. Thus, it may result in impairment of HBV-DNA recognition and subsequently disruption of immune responses. These results suggest a plausible mechanism which may partially define the fact that immune responses are impaired in CHB patients.

Decreased expression of toll like receptor signaling molecules in chronic HBV infected patients.

INTRODUCTION: Toll like receptors (TLRs) and their signaling molecules play important roles in microbe recognition and induction of immune responses, including production of inflammatory cytokines, against viral infections. Therefore, the aim of this study was to examine expression levels of TLR signaling molecules (IRAK1, IRAK4, TRAF3, and IRF7) and the pro-inflammatory cytokines, IL-12 and IL-6 in chronic HBV infected (CHB) patients. DESIGN: This study was performed on 60 CHB patients and 60 healthy controls and the expression of IRAK1, IRAK4, TRAF3, and IRF7 and their downstream inflammatory cytokines (IL-12 and IL-6) were evaluated by Real-Time PCR and ELISA techniques. RESULTS: The results demonstrated that expression of IRAK4, TRAF3, and IRF7 were significantly decreased in PBMCs of CHB patients in comparison to healthy controls. Serum levels of IL-12 were significantly increased, while, IL-6 were not differ between patients and controls. CONCLUSIONS: Based on the results presented here it seems that CHB patients do not express appropriate levels of the genes in the TLRs pathway which may lead to impaired immune responses against HBV infection which is seen in the patients.