Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) has been shown to affect the progression of various inflammatory disorders, including pancreatitis. To investigate the role of MCP-1 in acute pancreatitis and to seek possible therapeutic means, we evaluated the effect of a plasmid expression vector containing a dominant-negative mutant MCP-1 gene (mMCP-1).


METHODS
Two rat models of acute pancreatitis were employed that used either cerulein (for mild pancreatitis) or a mixture of 5% taurocholic acid and trypsin (for severe pancreatitis). At 6 h after induction of acute pancreatitis with or without injection of mMCP-1, serum amylase levels and cytokine levels, as well as morphological evaluation of the pancreas, were determined. Survival rates were also evaluated.


RESULTS
Severe pancreatitis was significantly reduced by mMCP-1 injection. mMCP-1 decreased serum levels of amylase, IL-6, IL-10, and LDH, and improved the survival rate 48 h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1.


CONCLUSIONS
MCP-1 appears to be involved in the progression of severe forms of acute pancreatitis. Our data suggested that MCP-1 is a candidate as a therapeutic target to treat acute pancreatitis.
Ishibashi
Toshiaki
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Zhao
Haifeng
H
Kawabe
Ken
K
Oono
Takamasa
T
Egashira
Kensuke
K
Suzuki
Koichi
K
Nawata
Hajime
H
Takayanagi
Ryoichi
R
Ito
Tetsuhide
T
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002108:Ceruletide / Q000633:toxicity; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000097:blood; D016207:Cytokines; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000008:administration & dosage*; D007267:Injections; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D016896:Treatment Outcome
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D002108:Ceruletide