Neutrophil depletion--but not prevention of Kupffer cell activation--decreases the severity of cerulein-induced acute pancreatitis.
OBJECTIVE
To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis.


METHODS
Mice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride (GdCl3) to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. Myeloperoxidases (MPO) assessed neutrophil infiltration. Interleukin-6 (IL-6) and IL-10 were measured in serum, pancreas, lungs and liver.


RESULTS
In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCl3 had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects.


CONCLUSIONS
Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.
Laboratoire de Physiopathologie Hépatique et Imagerie Moléculaire, Hôpitaux Universitaires de Genève, 24 Rue Micheli-du-Crest, 1205 Geneva, Switzerland. catherine.pastor@hcuge.ch
Catherine M
CM
Pastor
Alain
A
Vonlaufen
Fabianna
F
Georgi
Antoine
A
Hadengue
Philippe
P
Morel
Jean-Louis
JL
Frossard
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002452:Cell Count; D002108:Ceruletide; D005682:Gadolinium / Q000494:pharmacology; D007378:Interleukins / Q000032:analysis / Q000097:blood; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D009195:Peroxidase / Q000032:analysis; D011897:Random Allocation; D012720:Severity of Illness Index
D007378:Interleukins; D002108:Ceruletide; D005682:Gadolinium; D009195:Peroxidase; D000681:Amylases; C038958:gadolinium chloride