Title:Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in
Rat Model by Altering the Expression of Toll-Like Receptor-4,
Interleukin-2, and Tumor Necrosis Factor-α
Volume: 23
Issue: 1
Author(s): Moustafa M. Mohammed, Ahmed M. M. Okasha, Amany H. Abdel Naiem, Reham F. Mohamed, Sayed F. Abdelwahab*Hatem A. Mohamed
Affiliation:
- Department of Pharmaceutics and Industrial Pharmacy, College of
Pharmacy, Taif University, Al-Haweiah, PO Box 11099, Taif 21944, Saudi Arabia
Keywords:
Autoimmune hepatitis, cyclosporine, interleukin 2, NFkB, TLR-4, TNF-a.
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 α (TNF-α) 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-α 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.
