Treatment with anti-factor VIIa in acute pancreatitis in rats: blocking both coagulation and inflammation?
OBJECTIVE
Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active-site-inactivated factor VIIa, have shown anti-inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome (MODS) in severe acute pancreatitis.


METHODS
Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N-acetyl-cysteine and active-site-inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL-6 and MIP-2, were measured using ELISA.


RESULTS
Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N-acetylcysteine and active-site-inactivated factor VIIa. Levels of interleukin-6 and macrophage inflammatory protein-2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels.


CONCLUSIONS
Both N-acetylcysteine and active-site-inactivated factor VIIa showed powerful anti-inflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.
Andersson
Ellen
E
Department of Surgery, Lund University Hospital, Lund, Sweden.
Axelsson
Jakob
J
Pedersen
Lars Christian
LC
Elm
Torben
T
Andersson
Roland
R
D000208:Acute Disease; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D054426:Chemokine CXCL2; D004797:Enzyme-Linked Immunosorbent Assay; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D015846:Monokines / Q000097:blood; D018384:Oxidative Stress; D010195:Pancreatitis / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D054426:Chemokine CXCL2; D015850:Interleukin-6; D015846:Monokines; D009195:Peroxidase; D015942:Factor VIIa