Organ Failure due to Systemic Injury in Acute Pancreatitis

Neutrophils:
Leukocytosis (>12000/mm
3
) is part of the SIRS criteria
81
, and is an early predictor of 
severity of AP
2
. The leukocytosis in early pancreatitis is predominantly neutrophilic, and 
several studies have shown that depletion of neutrophils reduces inflammatory cell 
infiltration (e.g. reduced MPO) into the lungs and improves microvascular 
permeability
52, 65, 82, 83
. Neutrophil infiltration into an organ is dependent on their adhesion 
to the endothelium, mediated by P- and E-selectin on the surface of endothelial cells. These 
bind adhesion molecules like L-selectins and integrins on the surface of neutrophils. Blood 
levels of P- and E-selectin were elevated in rodent
84
and in human
85
AP. These respectively 
correlated with severity of AP and lung injury. Interestingly, trypsin generation in the late 
phase of experimental pancreatitis has been shown to be neutrophil dependent
65
, and trypsin 
can also stimulate neutrophils to secrete matrix metalloproteinase-9. Based on these 
observations, trypsin mediated lung injury has been hypothesized to be neutrophil 
dependent. Other studies have shown that neutrophil infiltration into the lungs is due to the 
chemokines CXCL2 and CXCL4, and that their neutralization reduces lung inflammation
86
. 
However, neutrophils also have physiologic roles and their accumulation in the lungs, such 
as by increasing KC/CXCL1
87-89
expression does not cause damage, but conversely protects 
from fungal and bacterial infections. Moreover, neutropenia predisposes to infections
90-92
. 
Garg and Singh
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Gastroenterology. Author manuscript; available in PMC 2020 May 01.
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Therefore, it remains to be seen whether interference in neutrophil recruitment or their 
depletion during AP will improve systemic injury in human AP.