Chronic hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion and apoptosis to potentially assist viral persistence inside the host, eventually leading to exacerbated conditions of inflammation and hepatocarcinogenesis. Growing evidence suggests that spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs) could be one of the potential immune impairment mechanisms in chronic viral infection. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an essential role in regulating immune and inflammatory responses. Owing to its known role in priming T cell growth, differentiation, and inhibition of lymphocyte apoptosis, we investigated the protective effect of IL-6 in rescuing lymphocytes from apoptosis and functional exhaustion in chronic HCV infection. The expression pattern of antiapoptotic (Mcl-1 and Bcl-2), proapoptotic (caspase-3 and Bim) genes along with interferon gamma (IFN-γ) and T cell inhibitory receptor (TIM-3) was analyzed before and after in vitro IL-6 treatment of patient-derived PBMCs. It was observed that the expression of antiapoptotic genes, Mcl-1 and Bcl-2 increased (threefolds and twofolds, respectively) and there was a considerable downregulation in T cell inhibitory receptor (TIM-3) and caspase-3. Similarly, the capacity of PBMCs to produce IFN-γ was also significantly increased (p < 0.001) depicting the promising nature of IL-6 in enhancing lymphocyte effector function. Summing it up, the study supports the positive role of IL-6 in rescuing PBMC population; however, the cytokine alone is not sufficient to sustain the adaptive immunity. It could be used as a potential candidate for combinational therapy along with other regulatory factors for ex vivo enhancement of lymphocyte and may help in moving one step toward adoptive T cell therapy in chronic HCV infection.
Keywords: IL-6; PBMCs; apoptosis; chronic HCV infection; exhaustion.