The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats.
BACKGROUND
Pancreatic and neutrophil elastase can aggravate or induce acute pancreatitis. Although increased elastase levels in the plasma of pancreatitis patients and animal models have been reported, the mechanism by which elastase is involved in the pathogenesis of acute pancreatitis has not yet been elucidated. We aimed to investigate the effects and the possible mechanism of a new human leukocyte elastase inhibitor (recombinant guamerin) in the treatment of cerulein-induced acute pancreatitis in rats.


METHODS
Fifty Sprague-Dawley rats were divided into three groups: a saline-infused control group (I), a cerulein-induced acute pancreatitis group (II), and a cerulein plus guamerin infusion group (III). Guamerin (1-2 micromol/kg/h) was infused continuously in group III. The severity of pancreatitis was determined biochemically, histologically, and by cytokine changes between groups I, II and III.


RESULTS
Significant differences in serum amylase, lipase, and pancreatic wet weight were observed in each group, respectively (group I; 2346.2 IU/L, 9.9 IU/L, 1.4+/-0.3 g, group II; 13,596.8 IU/L, 7439.4 IU/L, 2.2+/-0.5 g, group III; 9443.2 IU/L, 4516.3 IU/L, 1.7+/-0.6 g). Serum IL-6 and TNF-alpha [AU1]level peaked 1-4 h and 1-2 h. After the induction of pancreatitis, IL-6 and TNF-alpha levels were decreased in group III than group II, (group I; 13.1/4.0 pg/mL, group II; 198.5/63.2 pg/mL, group III; 102.1/13.1 pg/mL), but no significant difference in IL-1beta was observed. Histologic gradings and severity, such as vacuolization, inflammation, lobular disarray, and edema of the pancreas, were significantly lower in the cerulein plus guamerin infusion group III.


CONCLUSIONS
Recombinant guamerin, a new human leukocyte elastase inhibitor, may decrease the severity of pancreatitis and diminish pancreatic acinar cell injury by inhibition of neutrophilic infiltration and cytokine activation in the initial stage of cerulein-induced acute pancreatitis in rats.
Jo
Yun Ju
YJ
Department of Internal Medicine, Eulji University College of Medicine, 280-1 Hagye 1-Dong, Nowon-Gu, Seoul 139-711, South Korea.
Choi
Ho Soon
HS
Jun
Dae Won
DW
Lee
Oh Young
OY
Kang
Joo Seop
JS
Park
Il Gyu
IG
Jung
Kyung Hwan
KH
Hahm
Joon Soo
JS
D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D016207:Cytokines / Q000097:blood; D016670:Gabexate / Q000627:therapeutic use; D006023:Glycoproteins / Q000627:therapeutic use; D007447:Invertebrate Hormones / Q000627:therapeutic use*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D016207:Cytokines; D006023:Glycoproteins; D007447:Invertebrate Hormones; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; C093975:guamerin; D016670:Gabexate; D002108:Ceruletide; D000681:Amylases; D019272:Leukocyte Elastase; C028665:urinastatin