Targeting peripheral immune response reduces the severity of necrotizing acute pancreatitis.
OBJECTIVE
A complex cascade of immunologic events leads to the development of systemic inflammatory response in acute pancreatitis (AP). Our aim was to evaluate the effects of two different immunomodulating treatments: Dexamethasone (Dx) and N-acetylcysteine (NAC), on the progression of necrotizing AP.


METHODS
Prospective, random, and control study. Laboratory animals.


METHODS
University-based research laboratory.


METHODS
Male Wistar rats.


METHODS
Retrograde infusion of 3.5% of sodium taurocholate into pancreatic-biliary duct was used to induce AP in rats. Dx (1 mg/kg) was administered 30 mins before or 1 hr after AP, and NAC (50 mg/kg) was given 1 hr before and 1 hr after inducing AP.


RESULTS
Dx and NAC treatments reduced the severity of AP in terms of amylasemia, pancreatic edema, and pancreatic and liver necrosis. Dx, administered before or after AP, and NAC reduced the leukocytosis induced by AP and blocked the ability of circulating monocytes to produce tumor necrosis factor-alpha and monocyte chemoattractant protein-1; however none of them significantly reduced the overexpression of intercellular cell adhesion molecule-1 found in monocytes 6 hrs after inducing AP. Leukocyte infiltration in the pancreas was attenuated in Dx-pretreated rats and significantly reduced 6 hrs after inducing AP in rats treated with NAC. However, neither Dx nor NAC were able to significantly reduce interleukin-6 in plasma or mitigate leukocyte infiltration in the lung.


CONCLUSIONS
Our data demonstrated that treatments targeting the peripheral immune response reduced the severity of sodium taurocholate -induced AP attenuating pancreatic and liver injury, but they were not effective for limiting the spread of the inflammatory damage to the lung.
Yubero
Sara
S
Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.
Ramudo
Laura
L
Manso
Manuel A
MA
De Dios
Isabel
I
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000276:immunology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D000111:Acetylcysteine