A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits

Gut. 1998 Aug;43(2):232-9. doi: 10.1136/gut.43.2.232.

Abstract

Background: Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.

Aims: To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.

Methods: Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.

Results: Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor alpha (TNF-alpha) from three to six hours after induction of acute pancreatitis (p = 0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-alpha, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.

Conclusion: WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-alpha, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylases / blood
  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / immunology
  • Ascitic Fluid / metabolism
  • Blood Glucose / analysis
  • Calcium / blood
  • Female
  • Immunohistochemistry
  • Interleukin-8 / immunology*
  • Lipase / blood
  • Lung Diseases / immunology*
  • Male
  • Neutrophils / immunology
  • Pancreatitis, Acute Necrotizing / blood
  • Pancreatitis, Acute Necrotizing / chemically induced
  • Pancreatitis, Acute Necrotizing / immunology*
  • Rabbits
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Blood Glucose
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Lipase
  • Amylases
  • Calcium