Rapamycin Prevents Con A-induced Liver Injury By Inhibiting Lymphocyte Proliferation

Background and Aims: Concanvalin A(Con A),is a kind of lectin separated from sword bean. In l992, Tiegs G et al. found Con A i.v. injection would induce a T cell-dependent hepatitis in mice. Now liver injury induced by Con A is often used as a model to study the pathophysiology of immune mediated liver injury. Rapamycin (Rapa) is an effective immunosuppressant widely used for preventing immune activation and transplant rejection. Here we examined the effect of Rapa on liver injury caused by Con A has not been carefully examined.Methods: Mice received intraperitoneal Rapa injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the level of cytokines was detected by Enzyme Linked Immunosorbent Assay (ELISA). To observe the activation of lymphocytes, lymphocytes were stained with anti-CD69 Abs and cells were analyzed by flow cytometry. For the intracellular cytokine assay, lymphocytes were fixed, permeabilized, and stained with intracellular anti-IL-4,IFN-γand TNF-αAbs. Cells are analyzed by flow cytometry. Cells were labeled by proliferation cell nuclear antigen( PCNA) in immunohistochemistry to assess cells proliferation.Results: In the present study, we examined the effect of Rapa on liver injury following Con A injection in the mouse. We found that treatment of mice with Rapa protected the liver from Con A-induced injury. Pretreatment with Rapa dramatically ameliorated Con A-induced mortality. This protection was associated with reduced transaminase levels in the blood and further confirmed by liver histology. ELISA revealed that Rapa production as compared to and TNF-αsuppressed pro-inflammatory cytokines IFN-γthe untreated controls. Furthermore, intra-hepatic lymphocyte proliferation was significantly inhibited.Conclusion: These findings suggested that Rapa has the therapeutic potential for treatment of immune-mediated liver injury in the clinic.