Effects and mechanism of the etanercept on pancreatic encephalopathy

Lv,Yifan; Jing,Guojie; Zhu,Gang; Luo,Honghai; Li,Baisheng; Xie,Yituan; Li,Caiming; Wang,Xiangyu

doi:10.3892/mmr.2020.11062

Effects and mechanism of the etanercept on pancreatic encephalopathy

Authors:
- Yifan Lv
- Guojie Jing
- Gang Zhu
- Honghai Luo
- Baisheng Li
- Yituan Xie
- Caiming Li
- Xiangyu Wang
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Affiliations: Department of Neurosurgery, Medical College, Jinan University, Guangzhou, Guangdong 510220, P.R. China, Department of Neurosurgery, Huizhou First People's Hospital, Huizhou, Guangdong 516000, P.R. China, Department of Neurosurgery, Huizhou Central People's Hospital, Huizhou, Guangdong 516000, P.R. China, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510220, P.R. China
Published online on: April 8, 2020 https://doi.org/10.3892/mmr.2020.11062
Pages: 2615-2623

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Abstract

Pancreatic encephalopathy (PE) is a common fatal complication of acute pancreatitis (AP). Proinflammatory cytokines such as tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 are generated during AP, and act synergistically to promote PE and multisystem failure. Caerulein‑induced AP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TNF‑α inhibitor etanercept in PE models and elucidate the regulatory mechanisms. To model PE in vitro, rat hippocampal H19‑7/IGF‑IR neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model PE in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. At 6 h after administration, it was noted that etanercept downregulated expression of TNF‑α, IL‑1β and IL‑6 by negatively regulating NF‑κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. Conversely, etanercept promoted the expression of the neurotrophic and anti‑inflammatory hypoxia‑inducible factor 1 α (HIF‑1α). In rat hippocampus, etanercept also reduced the levels of TNF‑α, IL‑1β and IL‑6, upregulated HIF‑1α expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein‑induced PE, at least in part via suppression of NF‑κB signaling and alleviation of oxidative stress.

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