Effect of diet-induced obesity on acute pancreatitis induced by administration of interleukin-12 plus interleukin-18 in mice.
Obesity is associated with increased severity of acute pancreatitis (AP). We recently developed a model of AP induced by administration of interleukin (IL)-12+IL-18, two cytokines that are elevated in patients with AP. In this model, severe AP develops in obese leptin-deficient ob/ob mice compared to lean littermates. In the present report, we evaluated the pancreatic response of diet-induced obesity (DIO) mice to IL-12+IL-18. Body weight loss and adipose tissue necrosis were more severe and prolonged in cytokine-injected DIO compared to lean mice. Edematous AP developed in lean mice, whereas DIO mice developed necrotizing AP. Obese DIO mice developed more severe hypocalcemia, increased liver damage and a heightened acute-phase response compared to lean mice, although leukopenia and thrombocytopenia were of comparable severity in lean and DIO mice. Serum levels of IL-6, IL-10, and IL-22 were significantly higher in DIO compared to lean mice, whereas interferon-gamma and tumor necrosis factor-alpha did not differ between the two groups. In conclusion, obesity induced by high-fat diet is associated with increased disease severity and duration in the model of AP induced by administration of IL-12+IL-18.
Pini
Maria
M
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.
Sennello
Joseph A
JA
Cabay
Robert J
RJ
Fantuzzi
Giamila
G
D000273:Adipose Tissue / Q000473:pathology*; D000276:Adjuvants, Immunologic; D000818:Animals; D016207:Cytokines / Q000008:administration & dosage / Q000097:blood*; D004032:Diet; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12; D020382:Interleukin-18; D007970:Leukopenia; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009765:Obesity / Q000097:blood / Q000150:complications*; D010195:Pancreatitis / Q000097:blood / Q000209:etiology* / Q000276:immunology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000150:complications / Q000276:immunology; D012720:Severity of Illness Index; D013921:Thrombocytopenia; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss
D000276:Adjuvants, Immunologic; D016207:Cytokines; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma
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