Matrix metalloproteinase-1 and cytokines in patients with acute pancreatitis.
BACKGROUND
Hypercytokinemia is known to occur in severe acute pancreatitis, suggesting that the production, deposition, and degradation of the extracellular matrix (ECM) occur actively as a result of the actions of the complicated cytokine network.


OBJECTIVE
To examine the influence of cytokines and growth factors on the ECM in acute pancreatitis from the points of view of the severity of the disease, the complication of multiple organ dysfunction syndrome (MODS), and the prognosis, 25 patients with acute pancreatitis were divided into three groups according to the severity of the condition as assessed by the Ranson score. The serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinases (TIMP)-1, the MMP-1.TIMP-1 complex, tumor necrosis factor (TNF)-alpha, and transfer growth factor (TGF)-beta1 were determined by enzyme-linked immunosorbent assay.


RESULTS
Comparison of the three groups divided according to the severity of the disease revealed significant differences in the levels of MMP-1 and TNF-alpha among the three groups, with the levels being higher in patients with more severe disease. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were found to be significantly lower in patients with more severe disease. Comparison between the group with the complication of MODS and the group without the complication showed that the levels of MMP-1, the MMP-1.TIMP-1 complex, and TNF-alpha were significantly higher in the former group than in the latter group. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were significantly lower in the group with the complication of MODS than in the group without the complication. Comparison between the nonsurvivor group and the survivor group revealed significantly higher levels of MMP-1, TIMP-1, and TNF-alpha in the nonsurvivors than in the survivors. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were significantly higher in the survivors than in the nonsurvivors. A significant correlation was observed between MMP-1 levels and TNF-alpha levels. On the other hand, a significant negative correlation was noted between MMP-1 levels and TGF-beta1 levels.


CONCLUSIONS
The results of our study suggest that the activity of the ECM catabolic enzyme MMP-1 and cytokines are related to the development of acute pancreatitis.
Nakae
Hajime
H
Department of Emergency and Critical Care Medicine, Akita University School of Medicine, Akita, Japan.
Endo
Shigeatsu
S
Inoue
Yoshihiro
Y
Fujino
Yasuhisa
Y
Wakabayashi
Go
G
Inada
Katsuya
K
Sato
Shigehiro
S
D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood* / Q000473:pathology; D012720:Severity of Illness Index; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1