Abstract
Background: Autoimmune hepatitis (AIH) is an inflammatory liver disease that is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor a (TNF-alpha) are potent inflammatory cytokines secreted in AIH, playing an important role in the early development of inflammation and hepatocyte damage.
Objectives: This study examined the role of cyclosporine in AIH and illustrated its actions on altered hepatic function in the silica-induced AIH model.
Methods: AIH was induced in Wistar rats using sodium silicate. The rats were divided into four groups: the control group, silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4 and IL-2 mRNA expressions in liver tissues were tested by RTPCR.
Results: AIH was associated with up-regulation of liver enzymes, IL-2 and TLR-4 gene expression, while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1 +/- 0, 13.57 +/- 1.91, 4 +/- 0.38, and 2 +/- 0 in control, AIH, cyclosporine, and prevention groups, respectively (p< 0.001). Also, the relative quantity of IL-2 mRNA was 1 +/- 0, 14.79 +/- 1.42, 7.07 +/- 0.96, and 3.4 +/- 0.55 in control, AIH, cyclosporine, and prevention groups, respectively (p< 0.001). Additionally, immunohistochemical staining for TNF-a in liver sections was increased in the silica-AIH group but was found to decrease in the cyclosporine-treated and prevention groups.
Conclusion: This study advocates the therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.