PhD Scientific Days 2023

Pharmaceutical Sciences - Posters E

IL‑1β inhibition prevents diastolic dysfunction development, but lacks hepatoprotective effect in an aged mouse model of NASH

Text of the abstract

Introduction: Interleukin-1β (IL-1β) is a key mediator in the pathophysiology of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of inflamm-aging. IL-1β contributes to cardio-metabolic decline, and may even have crucial effect on hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies.
Aims: We aimed to investigate the hepatic and cardiac effects of anti-IL-1β monoclonal antibody treatment in an aged animal model of NASH.
Methods: 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional—and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR.
Results: Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH.
Conclusion: IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.
Funding: The work was supported by the European Union’s Horizon 2020 No. 739593, Momentum Research Grant, TKP/ITM/NKFIH, OTKA-FK-134751, ÚNKP-21-3-II, EFOP-3.6.3.-VEKOP-16-2017-00009, ‘Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése.