Immune status and inflammatory response differ locally and systemically in severe acute pancreatitis.
OBJECTIVE
Acute pancreatitis (AP) is an inflammatory disorder that develops a complex cascade of immunological events. The local and systemic immune status and inflammatory response might contribute to the understanding of underlying pathophysiological mechanisms and potential treatment.


METHODS
Severe AP was induced by intraductal perfusion of 5% sodium taurodeoxycholate in rats. mRNA expression of cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and NF-kappaB activation was assessed by electrophoretic mobility shift assay in fresh pancreatic acini and circulating monocytes 1, 3, 6 or 9 h after sham operation, induction of AP or N-acetylcysteine (NAC) pretreatment. Flow cytometry was performed on cells obtained from the peripheral blood.


RESULTS
An inverse relationship in pancreatic and circulating monocytic NF-kappaB activation was detected 6 and 9 h after induction of AP. NAC further suppressed monocytic NF-kappaB activation induced by AP as seen 9 h after induction of AP. A marked constitutive increase in the expression of IL-6, CINC and MCP-1 was seen in pancreatic acini, whereas no change in mRNA expression of inflammatory mediators was observed in circulating monocytes 6 h after induction of AP. Flow cytometry further confirmed the altered function of circulating monocytes.


CONCLUSIONS
The different immune status and inflammatory response in the pancreas and circulating monocytes improve the understanding of the mechanisms by which systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop in severe AP. A potential therapeutic approach could be to restore the functional capacity of the immune system in AP. The use of an NF-kappaB inhibitor, preferentially reaching the local inflammatory foci, could be a potential future way of intervention.
Shi
Changbin
C
Department of Surgery, Lund University Hospital, Lund, Sweden.
Zhao
Xia
X
Lagergren
Anna
A
Sigvardsson
Mikael
M
Wang
Xiangdong
X
Andersson
Roland
R
D000111:Acetylcysteine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D039481:CD11b Antigen / Q000097:blood; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D009000:Monocytes / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry; D010195:Pancreatitis / Q000276:immunology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D039481:CD11b Antigen; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D017493:Leukocyte Common Antigens; D000111:Acetylcysteine