Hypertriglyceridemic
pancreatitis (HTGP) is often encountered clinically as a common form of recurrent
acute pancreatitis (AP). It is important to evaluate the management of severe
hypertriglyceridemia (HTG) or anti-
inflammation in the prophylaxis of HTGP in the clinic.
FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new
anti-inflammatory agent with low toxicity and reported to ameliorate
lung injury with
pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly
intraperitoneal injection of
cerulein in
apolipoprotein CIII transgenic mice with severe HTG.
FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of
FTY720 to protect against HTGP were assessed by serum
amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory
cytokine genes. As a result, injection of
cerulein resulted in more severe pathological changes of AP and higher
monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice.
FTY720 pretreatment improved the pathological severity of AP and decreased the expression of
monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However,
FTY720 did not affect plasma
triglyceride levels, and other inflammatory factors and plasma
amylase were not correlated with the extent of pancreatic damage in AP with or without
FTY720 administration. In summary, our study in a new model,
apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of
FTY720 can significantly attenuate
cerulein-induced AP and hence warrant further investigation of
sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP.