Effect of Exogenous Interleukin-10 on Carbon Tetrachloride CCL4-Induced Hepatic Fibrosis in Rats

Nasr El-Din, Wael; Hassan, Gamal M; Abdel-Hamed, Alaa El-Din S; Kamel, Amr A

doi:10.21608/scumj.2013.45657

Effect of Exogenous Interleukin-10 on Carbon Tetrachloride CCL4-Induced Hepatic Fibrosis in Rats

Document Type : Original Article

Authors

¹ Department of Anatomy, Faculty of Medicine, Suez Canal University, Egypt.

² Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Egypt.

³ Departments of Pathology, Faculty of Medicine, Suez Canal University, Egypt.

10.21608/scumj.2013.45657

Abstract

Background: Transforming growth factor β1 (TGF-β1) is one of the strongest profibrotic cytokines and TGF-β1/Smad signaling is the cardinal signal transduction pathway involved in fibrosis. Previous studies indicated that exogenous IL-10 down regulates collagen type I. It also exerts antifibrogenic effect by down regulating profibrogenic cytokines such as (TGF- β1). All these studies indicate that IL-10 might become a new therapeutic target. Aim: To investigate the potential therapeutic effect of exogenous interleukin-10 on reversing the well-established hepatic fibrosis of CCl₄ administration in experimental rats. Materials and Methods: Albino rats were divided into four groups (27 rats each): group A (control), group B1 (CCl₄-treated), group B2 (spontaneous recovery, SR) and group B3 (IL-10-treated). Rats' liver tissue was stained with i) hematoxylin and eosin (H & E) and, ii) Masson’s trichrome stains for evaluation of the histological activity index (HAI). Serum TGF-β1 was determined by ELISA. Results: No inflammation was found in the control group, however, marked inflammation (grade 3) was observed in CCl₄-induced fibrosis group while moderate inflammation (grade 2) was observed in SR group. Meanwhile the administration of IL-10 in group D resulted in a marked decrease in the grading of inflammation (grade 1) compared to CCl₄-induced fibrosis group.No fibrosis was observed in the control group, however, a marked fibrosis reaching to cirrhosis (stages 3&4) was observed in CCl₄-induced fibrosis group. The degree of fibrosis showed a mild decrease (stage 3) in SR group. Meanwhile the administration of IL-10 in group D resulted in a marked decrease in the stage of fibrosis to (stage 1).Serum TGF-β1 concentration dramatically increased in CCl₄-induced fibrosis group compared to the control group. It also increased in SR group, but lesser than CCl₄treated group while it was significantly reduced in the IL-10 treated group. Conclusions: Our results provide evidence towards the potential effect of IL-10 as anti-TGF-β1 that could lead to a reduction of hepatic fibrosis.

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