Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models

Abstract

Background/Aims: Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver whose pathogenic mechanisms have not yet been elucidated. Moreover, the current treatment used for the vast majority of AIH patients is largely dependent on immunosuppressant administration and liver transplantation. However, research on the pathogenesis of AIH and effective new treatments for AIH have been hampered by a lack of animal models that accurately reproduce the human condition. Methods: AIH models created by concanavalin A (ConA) injections at different times and doses. The levels of ALT, AST, LDH and inflammatory cytokines were examined at various times after 20 mg/kg ConA was administered by ELISA using commercially available kits. Moreover, liver pathological changes were observed by flow cytometry (FCM) and H&E staining. Results: Our experiments demonstrated that the levels of ALT, AST, LDH and several inflammatory cytokines, including TNF-α, IFN-γ, and IL-6, were higher in the 20 mg/kg 12 h ConA group than in the other groups. Importantly, the numbers of activated CD4⁺ and CD8⁺ T lymphocytes in the blood, spleen and liver were calculated. These results showed that ConA (20 mg/kg for 12 h)-induced hepatitis was similar to that in clinical AIH patients. Furthermore, we found that the number of MDSCs in the blood was significantly increased in the ConA (20 mg/kg for 12 h) group compared with controls. Our findings indicated that ConA (20 mg/kg for 12 h)-induced hepatitis could be used as an experimental murine model that mirrors most of the pathogenic properties of human type I AIH. Conclusion: This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

“…The EAH model was established at 12 h after an injection of ConA with a dose of 20 mg/kg through the tail vein, which was based on our previous study and other reported articles [11][12][13][14] . To evaluate the EAH model, the mice were divided into two groups: (1) Mice were given a single intravenous injection of normal saline as a vehicle control.…”

“…To investigate the role of cDCs in the pathogenesis of EAH, we developed a mouse model of ConA-induced AIH as in our previous study 11,14,19 . As shown by liver function and H&E, EAH was successfully established after ConA injection in EAH model ( Supplementary Fig.…”

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…Nonetheless, even though it is inconsistent with the potent anti-inflammatory action of IL37 in experimental studies, the hypothesis can neither be ruled out that the augmented levels of IL37 may play an unexpected pathogenetic role in these autoimmune diseases by activating unknown inflammatory pathways that have so far not been recognized to be modulated by IL37. Cytokines exerting primarily anti-inflammatory effects have subsequently been shown to be also capable of upregulating immunoinflammatory responses, as has been shown with endogenous IL4 in models of autoimmune hepatitis [29] and exogenously administered IL10 in models of orchitis [30]. Vice versa, anti-inflammatory effects of prototypical Th1 cytokines such as IFN-γ and also TNF-α have been reported in models of type 1 diabetes [31,32].…”

Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model

“…model to study this disease [3]. Concanavalin A (ConA) may induce a typical T cell-mediated hepatitis in mice characterized by immune cell infiltration and severe liver damage [4]. Many studies related to the pathophysiology of immunologically mediated hepatic disorders such as autoimmune chronic active hepatitis were based on this mouse model [5][6][7].…”

“…Over the past decades, several researchers have tried to establish appropriate animal models, but a widely accepted AIH mouse model has not yet been recognized [4,9,10]. AIH is divided into two main types based on the serological autoantibody profile: type-1 AIH and type-2 AIH [2].…”