Anti-4-1BB monoclonal antibodies attenuate concanavalin A‑induced immune‑mediated liver injury in mice

Xia,Guangtao; Wu,Sensen; Zhang,Yuanchao

doi:10.3892/etm.2016.3503

Anti-4-1BB monoclonal antibodies attenuate concanavalin A‑induced immune‑mediated liver injury in mice

Authors:
- Guangtao Xia
- Sensen Wu
- Yuanchao Zhang
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Affiliations: Department of Rheumatology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: June 24, 2016 https://doi.org/10.3892/etm.2016.3503
Pages: 1263-1268
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Effective therapies for the treatment of immune‑mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4‑1BB has a key role in T‑cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study was to evaluate the potential therapeutic or preventive function of an anti‑4‑1BB monoclonal antibody (mAb) in a mouse model of concanavalin (Con) A‑induced immune‑mediated liver injury. A mouse model of immune‑mediated liver injury was established by tail vein injection of Con A (20 mg/kg). 4‑1BB mAb (100 µg), with or without methylprednisolone (MEP; 3 mg/kg), was intraperitoneally injected into the tail vein 2 h prior to or 2 h following Con A injection. Con A induced marked hepatocyte necrosis, significantly reduced CD 4+/CD25+ T‑cell levels, and increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), in addition to the percentage of 4‑1BB+ T‑cells, compared with the control (all P<0.05). The administration of 4‑1BB mAb prior to or following Con A injection was able to attenuate Con A‑induced liver tissue damage and significantly reduce serum AST and ALT levels (P<0.05). A combination of MEP and 4‑1BB mAb further reduced serum AST and ALT levels, compared with either treatment alone. In addition, administration of 4‑1BB mAb and MEP alone or in combination significantly increased CD4+/CD25+ T‑cell levels, compared with the control (P<0.05). These results suggested that 4‑1BB mAb was able to attenuate liver injury and preserve liver function in a mouse model of Con A‑induced immune‑mediated liver injury by promoting the expansion of CD4+/CD25+ T‑cells. Furthermore, a combination of 4‑1BB mAb with MEP was associated with greater beneficial effects than either treatment alone. The clinical significance of 4‑1BB mAb in immune‑mediated liver disease remains to be elucidated in future studies.

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