QS92. Adiponectin Modulates The Cytokine and Chemokine Milieu in Steatopancreatitis

Introduction: Obesity is epidemic and is an independent risk factor for the development of severe pancreatitis. The powerful anti-inflammatory adipokine adiponectin is decreased in obesity. We have recently shown that congenitally obese mice develop more severe cerulein-induced acute pancreatitis and have lower adiponectin levels than lean mice. We therefore hypothesized that adiponectin replacement would attenuate pancreatitis severity in obese mice (steatopancreatitis). Methods: 32 lean C57BL/6J and 16 congenitally obese Lepdb female mice were studied. At 12 weeks of age half the mice from each strain received supplemental adiponectin (1 mcg/g IP), and the remaining mice received vehicle. One hour later, pancreatitis was induced by cerulien injection (50mcg/kg IP hourly for six hours). Pancreatic tissue levels of pro-inflammatory cytokines IL-6 and IL-18, as well as the chemokine MCP-1 were measured by ELISA. Data were analyzed by ANOVA and Tukey tests, p<0.05 was considered significant. Results: Pancreatic tissue levels of IL-6, MCP-1, and IL-18 are presented in the Table. Conclusions: These data show that in acute pancreatitis: 1) IL-6 and MCP-1 were significantly increased in obese animals versus lean mice, and 2) in obese animals, adiponectin administration significantly decreased the chemokine MCP-1, but paradoxically increased the pro-inflammatory cytokine IL-18. We conclude that adiponectin plays an important role in modulating the cytokine and chemokine milieu of steatopancreatitis. Tabled 1 IL-6(pg/mg) MCP-1(pg/mg) IL-18(pg/mg) Lean - Vehicle 955 ± 126 6289 ± 757 1362 ± 77 Lean - Adiponectin 1264 ± 167 6599 ± 318 1156 ± 64 Obese - Vehicle 11682 ± 2161 ⁎ p<0.05 vs. Lean, 11075 ± 1076 ⁎ p<0.05 vs. Lean, 1167 ± 60 Obese - Adiponectin 11580 ± 2233 ⁎ p<0.05 vs. Lean, 8145 ± 1434 † p<0.05 vs. Obese Vehicle 1409 ± 105 † p<0.05 vs. Obese Vehicle p<0.05 vs. Lean, † p<0.05 vs. Obese Vehicle Open table in a new tab