Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis.
OBJECTIVE
Obesity is a negative prognostic factor in patients with critical illnesses such as acute pancreatitis (AP). The outcome of AP is determined by the severity of systemic inflammation and organ dysfunction. In a previous study, we found that AP caused more deaths in obese rats than in lean rats. In the present study, we examined whether the effect of obesity on rats with AP is associated with distinct alterations in inflammatory cytokine expression in organs involved in AP.


METHODS
AP was induced in lean and obese Zucker rats by pancreatic infusion of taurocholic acid. All survivors were killed 8 h later. Gene transcripts for two proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)) and two anti-inflammatory cytokines (IL-10 and pancreatitis-associated protein (PAP)) were determined in the pancreas, liver, and lungs by quantitative real-time polymerase chain reaction. The severity of AP was assessed by means of histology and serology.


RESULTS
Obese AP rats had higher TNF-alpha mRNA in all organs examined, lower IL-10 and IL-6 mRNA in the pancreas, and lower PAP mRNA in the liver, compared to lean AP rats. Lean and obese AP rats had similar pancreatic lesions as assessed by histology. However, steatohepatitis and increased serum alanine amino transferase levels, which are indications of hepatic injury, were present in obese but not lean AP rats.


CONCLUSIONS
Our findings suggest that altered inflammatory cytokine expression and increased vulnerability in the liver underlie the detrimental influence of obesity on AP.
Segersvärd
Ralf
R
Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden. ralf.segersvard@ki.se
Tsai
Jon A
JA
Herrington
Margery K
MK
Wang
Feng
F
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C000612144:Reg3b protein, rat; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013656:Taurocholic Acid; D000410:Alanine Transaminase