Gut 2000;47:838-844 ( December )

Article

Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury M Bhatia^a, M Brady^a, J Zagorski^d, S E Christmas^b, F Campbell^c, J P Neoptolemos^a, J Slavin^a

^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

BACKGROUNDLung 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.


Keywords: chemokines; acute pancreatitis; caerulein; adult respiratory distress syndrome

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© 2000 by Gut
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