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a Department of
Surgery, University of Liverpool, Royal Liverpool University Hospital,
Liverpool, UK, b Department of Immunology,
University of Liverpool, Royal Liverpool University Hospital,
Liverpool, UK, c Department
of Pathology, University of Liverpool, Royal Liverpool University
Hospital, Liverpool, UK, d David
Axelrod Institute, Wadsworth Center, Albany, New York, USA
Correspondence to: Dr M Bhatia, Department of Surgery, University of Liverpool, 5th Floor UCD Building, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, UK. mbhatia{at}liverpool.ac.uk
Accepted for publication 22 June 2000
BACKGROUND
Lung injury
manifest clinically as adult respiratory distress syndrome (ARDS) is a
common cause of morbidity and mortality following acute pancreatitis
(AP). Neutrophils play a critical role in the progression of AP to
ARDS. C-x-C chemokines are potent neutrophil chemoattractants and
activators and have been implicated in AP.
AIMSTo evaluate the
effect of blocking the C-x-C chemokine, cytokine induced neutrophil
chemoattractant (CINC), in AP on pancreatic inflammation and the
associated lung injury in rats.
METHODSAP was induced
by hourly intraperitoneal injections of caerulein. Goat anti-CINC
antibody was administered either before or after starting caerulein
injections to evaluate the prophylactic and therapeutic effects,
respectively. Severity of AP was determined by measuring plasma
amylase, pancreatic water content, and pancreatic myeloperoxidase (MPO)
activity as a measure of neutrophil sequestration in the pancreas. Lung
injury was determined by measurement of pulmonary microvascular
permeability and lung MPO activity.
RESULTSTreatment with
anti-CINC antibody had little effect on caerulein induced pancreatic
damage. However, it reduced the caerulein mediated increase in lung MPO
activity as well as lung microvascular permeability when administered
either prophylactically (lung MPO (fold increase over control):
1.53 (0.21) v 3.30 (0.46), p<0.05; microvascular permeability (L/P%): 0.42 (0.07)
v 0.77 (0.11), p<0.05) or therapeutically
(lung MPO (fold increase over control): 2.13 (0.10)
v 4.42 (0.65), p<0.05; microvascular
permeability (L/P%): 0.31 (0.05) v 0.79 (0.13), p<0.05).
CONCLUSIONTreatment
with anti-CINC antibody afforded significant protection against
pancreatitis associated lung injury. These results suggest that CINC
plays an important role in the systemic inflammatory response in AP.
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