RT Journal Article
SR Electronic
T1 Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 100
OP 111
DO 10.1136/gutjnl-2014-308043
VO 65
IS 1
A1 Pawan Noel
A1 Krutika Patel
A1 Chandra Durgampudi
A1 Ram N Trivedi
A1 Cristiane de Oliveira
A1 Michael D Crowell
A1 Rahul Pannala
A1 Kenneth Lee
A1 Randall Brand
A1 Jennifer Chennat
A1 Adam Slivka
A1 Georgios I Papachristou
A1 Asif Khalid
A1 David C Whitcomb
A1 James P DeLany
A1 Rachel A Cline
A1 Chathur Acharya
A1 Deepthi Jaligama
A1 Faris M Murad
A1 Dhiraj Yadav
A1 Sarah Navina
A1 Vijay P Singh
YR 2016
UL http://gut.bmj.com/content/65/1/100.abstract
AB Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators.Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat.Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat.Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.