Specific type IV phosphodiesterase inhibitor ameliorates cerulein-induced pancreatitis in rats.
OBJECTIVE
Type IV phosphodiesterase is a key enzyme to metabolize intracellular adenosine 3',5'-cyclic monophosphate (cAMP) expressed in inflammatory cells. The specific type IV phosphodiesterase inhibitor that increases intracellular cAMP is known to be potent suppressor of proinflammatory cytokines. However, the effect of phosphodiesterase inhibitors on the development of pancreatitis has not been well understood. In the present study, we examined the effect of a specific type IV phosphodiesterase inhibitor on experimentally induced pancreatitis.


METHODS
Severity of cerulein-induced pancreatitis and pancreatic proinflammatory cytokine levels were studied with or without pretreatment with a specific type IV phosphodiesterase inhibitor (rolipram) in Sprague-Dawley rats.


RESULTS
Administration of rolipram clearly ameliorated severity of pancreatitis evaluated by edema, serum amylase (P<0.05), and lipase levels (P<0.05) in rats. Also, the level of pancreatic proinflammatory cytokine (interleukin-1beta (IL-1beta)) was significantly reduced when rats were treated with rolipram prior cerulein injection (P<0.05).


CONCLUSIONS
Our results demonstrated that intracellular cAMP and pancreatic proinflammatory cytokine level, which are regulated by type IV phosphodiesterase, might play an important role in the pathogenesis of acute pancreatitis.
Sato
Toshihiro
T
Department of Internal Medicine-1, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Otaka
Michiro
M
Odashima
Masaru
M
Kato
Sayuri
S
Jin
Mario
M
Konishi
Noriaki
N
Matsuhashi
Tamotsu
T
Watanabe
Sumio
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002108:Ceruletide; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram