Restoration of IL-۱۱ and IL-۱۵ cytokine production post calcium modulators and ROS treatment can assist viral clearance both in vitro and in vivo

Objective(s): Hepatitis B virus (HBV) infection alters the cytokines production to establish persistent infection. A reversion of cytokines back to their normal state can be a promising therapeutic approach to establish an optimal host immune response. Materials and Methods: We investigated the alteration in expression of IL-۱۵ and IL-۱۱ after HBV infection in vitro and in vivo in PBMCs of ۶۳ individuals divided into various HBV-infected patient groups. The mRNA expression was evaluated post-anti-oxidant and calcium modulators treatment by Real-time qPCR. Results: In vitro mRNA expression of both cytokines, post-infection was down-regulated considerably. Interestingly, in line with in vitro results, both cytokines’ in vivo expression was intensively down-regulated in chronic HBV-infected individuals rather than healthy controls. Both cytokines’ expression was up-regulated in cases of recovery compared with the inactive carriers and chronic HBV-infected individuals. IL-۱۵ mRNA expression was significantly up-regulated in both cell lines post EGTA and Ru۳۶۰ treatment while a significant increase was observed in the HepAD۳۸ cell line with NAC and BAPTA treatment. IL-۱۱ mRNA expression was significantly up-regulated in the HepG۲ cell line after all modulator treatments, whereas in the HepAd۳۸ cell line it was observed after BAPTA treatment. Our results thus indicate that viral infection tends to down-regulate the expression of cytokines and an in vivo up-regulation is an indication of recovery. Conclusion: Treatment of anti-oxidants and calcium modulators has resulted in the successful restoration of these cytokines thus pointing towards the use of calcium modulators to boost natural antiviral cytokine production. 

Keywords:

Hepatitis B virus , Interleukin-۱۱ , Interleukin-۱۵ , Hepatocellular carcinoma , Reactive Oxygen Species