title: Role of liver in modulating the release of inflammatory cytokines involved in lung and multiple organ dysfunction in severe acute pancreatitis.
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.
authors.affiliation: 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.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiyan
authors.initials: W
authors.lastname: Liu
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Sheng
authors.forename: Yaofei
authors.initials: Y
authors.lastname: Pei
authors.forename: Ruoqing
authors.initials: R
authors.lastname: Lei
authors.forename: Shengdao
authors.initials: S
authors.lastname: Zhang
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
mesh_terms: D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D010195:Pancreatitis / Q000150:complications*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid