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  • Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury

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Pancreas
Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury
  1. M Bhatiaa,
  2. M Bradya,
  3. J Zagorskid,
  4. S E Christmasb,
  5. F Campbellc,
  6. J P Neoptolemosa,
  7. J Slavina
  1. aDepartment of Surgery, University of Liverpool, Royal Liverpool University Hospital, Liverpool, UK, bDepartment of Immunology, University of Liverpool, Royal Liverpool University Hospital, Liverpool, UK, cDepartment of Pathology, University of Liverpool, Royal Liverpool University Hospital, Liverpool, UK, dDavid Axelrod Institute, Wadsworth Center, Albany, New York, USA
  1. 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

Abstract

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.

AIMS To 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.

METHODS AP 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.

RESULTS Treatment 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).

CONCLUSION Treatment 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.

  • chemokines
  • acute pancreatitis
  • caerulein
  • adult respiratory distress syndrome

  • Abbreviations used in this paper

    AP
    acute pancreatitis
    ARDS
    adult respiratory distress syndrome
    MPO
    myeloperoxidase
    MODS
    multiple organ dysfunction syndrome
    SIRS
    systemic inflammatory response syndrome IL-8, interleukin-8
    CINC
    cytokine induced neutrophil chemoattractant
    FITC
    fluorescein isothiocyanate

    • https://doi.org/10.1136/gut.47.6.838

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    • Abbreviations used in this paper

      AP
      acute pancreatitis
      ARDS
      adult respiratory distress syndrome
      MPO
      myeloperoxidase
      MODS
      multiple organ dysfunction syndrome
      SIRS
      systemic inflammatory response syndrome IL-8, interleukin-8
      CINC
      cytokine induced neutrophil chemoattractant
      FITC
      fluorescein isothiocyanate
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