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

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Abstract

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.

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Abbreviations

ALT:

Alanine transaminase

ARDS:

Acute respiratory distress syndrome

COX-2:

Cyclooxygenase-2

DAO:

Diamine oxidase

DTT:

Dithiothreitol

EDTA:

Ethylenediamine tetraacetic acid

EMSA:

Electrophoretic mobility shift assay

ESAP:

Early severe acute pancreatitis

FAP:

Fulminant acute pancreatitis

TNF-α:

Tumor necrosis factor α

GdCl3:

Gadolinium chloride

HEPES:

Hydroxyethyl piperazine ethanesulfonic acid

IL-6:

Interleukin 6

LPS:

Lipopolysaccharide

MODS:

Multiple organ dysfunction syndrome

MOF:

Multi-organ failure

PDTC:

Pyrrolidine dithiocarbamate

PMSF:

Phenylmethylsulfonyl fluoride

SAP:

Severe acute pancreatitis

SD rat:

Sprague–Dawley rat

SIRS:

Systemic inflammatory response syndrome

The SO Group:

The sham operation group

SP:

Streptomycin avidin-peroxidase

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Acknowledgments

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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Authors and Affiliations

  1. Center for Organ Transplantation and Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 7W Surgical Building, 197 2nd Ruijin Road, Shanghai,  200025, China

    Yilin Wang, Xiqiang Liu, Meng Sheng, Yaofei Pei, Ruoqing Lei, Shengdao Zhang & Ran Tao

  2. Department of Surgery, Minhang District Central Hospital, Shanghai, China

    Yilin Wang & Weiyan Liu

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  1. Yilin Wang
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  2. Weiyan Liu
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  3. Xiqiang Liu
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  8. Ran Tao
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Correspondence to Ran Tao.

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Yilin Wang and Weiyan Liu have contributed equally to this study.

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Wang, Y., Liu, W., Liu, X. et al. Role of Liver in Modulating the Release of Inflammatory Cytokines Involved in Lung and Multiple Organ Dysfunction in Severe Acute Pancreatitis. Cell Biochem Biophys 71, 765–776 (2015). https://doi.org/10.1007/s12013-014-0261-5

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