Cell Biochemistry and Biophysics

, Volume 71, Issue 2, pp 765–776 | Cite as

Role of Liver in Modulating the Release of Inflammatory Cytokines Involved in Lung and Multiple Organ Dysfunction in Severe Acute Pancreatitis

  • Yilin Wang
  • Weiyan Liu
  • Xiqiang Liu
  • Meng Sheng
  • Yaofei Pei
  • Ruoqing Lei
  • Shengdao Zhang
  • Ran Tao
Original Paper


The objective of this study was to understand the role of liver in modulating remote organ dysfunction during severe acute pancreatitis (SAP). We used sodium taurocholate and endotoxin to induce SAP in the rats and confirmed the development of this condition by measuring serum and ascite levels of the biomarkers of liver and lung damage. Our results showed that expression of tumor necrosis factor (TNF)-α was up-regulated sequentially, first in the gut, then in the liver, and finally in lung. Moreover, the SAP-induced increase in the expressions of TNF-α and IL-6 occurring in gut, liver, and lung was directly related to the increase in time. However, in liver and lung, the transcriptional activity of NF-κB and expression of TNF-α at 4 and 8 h were not increased. The distribution sequence of the pro-inflammatory cytokines to various organs was determined by their detection in the blood from portal vein and inferior vena cava. Although liver received TNF-α during 0.5–8 h of the SAP induction, the release of this cytokine into vena cava was not increased in this period of time. In conclusion, our results suggest that the aggravation of SAP leading to development of MODS exhibited the gut-liver-lung cytokine axis. Furthermore, this study indicates that liver performs both protective and stimulatory activities in the modulation of pro-inflammatory cytokine generation and their distribution to remote organs, such as lungs.


Pancreatitis Hepatic function Inflammatory cytokine release NF-κB Endotoxin translocation 



Alanine transaminase


Acute respiratory distress syndrome




Diamine oxidase




Ethylenediamine tetraacetic acid


Electrophoretic mobility shift assay


Early severe acute pancreatitis


Fulminant acute pancreatitis


Tumor necrosis factor α


Gadolinium chloride


Hydroxyethyl piperazine ethanesulfonic acid


Interleukin 6




Multiple organ dysfunction syndrome


Multi-organ failure


Pyrrolidine dithiocarbamate


Phenylmethylsulfonyl fluoride


Severe acute pancreatitis

SD rat

Sprague–Dawley rat


Systemic inflammatory response syndrome

The SO Group

The sham operation group


Streptomycin avidin-peroxidase



This work was supported by a National Science Foundation Grant 81001324 (to RT), PhD site special research Grant from Ministry of Education 20100073120094 (to RT), “SMC-Rising Star Funding” from Shanghai Jiaotong University (to RT), and Endowed Professorship (“Oriental Scholar”) funding from Shanghai Municipal Science and Technology Committee (to RT).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yilin Wang
    • 1
    • 2
  • Weiyan Liu
    • 2
  • Xiqiang Liu
    • 1
  • Meng Sheng
    • 1
  • Yaofei Pei
    • 1
  • Ruoqing Lei
    • 1
  • Shengdao Zhang
    • 1
  • Ran Tao
    • 1
  1. 1.Center for Organ Transplantation and Department of Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of SurgeryMinhang District Central HospitalShanghaiChina

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