Aggravation of acute pancreatitis by heparan sulfate in mice.
OBJECTIVE
Systemic inflammatory response syndrome (SIRS) is responsible for pancreatitis-associated mortality, but its initiating events are poorly understood. Possible candidates may be endogenous substances, which have previously been shown to mediate inflammatory responses. The aim of this study was to investigate whether SIRS could be exaggerated by heparan sulfate (HS) in acute pancreatitis (AP).


METHODS
AP was induced in mice by cerulein injection and HS was administered one hour after the final cerulein injection. The severity of pancreatitis was assessed by serum amylase activity, pancreatic edema, and pancreatic myeloperoxidase (MPO) activity. Systemic inflammation was evaluated by assessing lung injury and by measuring serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Cytokine levels were also measured in pancreas and lung tissues.


RESULTS
HS did not worsen the pancreatic injury induced by cerulein. In contrast, HS exacerbated the systemic inflammation as measured by augmented lung MPO activity, increased lung TNF-alpha and IL-6 levels, and elevated serum IL-6 levels.


CONCLUSIONS
Our results indicate a potential role for HS in propagating pancreatic inflammation from a local process to a systemic response and thus suggest the possibility that blockade of HS might improve the outcome of SIRS in AP.
Liu
Hongxiang
H
Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China.
Li
Yuan
Y
Wang
Ling
L
Chen
Hongying
H
Guan
Jianting
J
Zhou
Zongguang
Z
D000818:Animals; D001707:Biopsy, Needle; D002108:Ceruletide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000009:adverse effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010186:Pancreatic Function Tests; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism*; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000401:mortality / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002108:Ceruletide; D016207:Cytokines; D006497:Heparan Sulfate; D009195:Peroxidase; D014409:Tumor Necrosis Factor-alpha