A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokineresponse and acute lung injury in experimental severe acute necrotisingpancreatitis in rabbits

摘要

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 α (TNF-α) 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-α, 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 theamount of pancreatic necrosis induced by injection of 5% bile acid,but does reduce the acute lung injury, presumably through inhibition ofcirculating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore,a role of IL-8 in the progression of acute pancreatitis and thedevelopment of its systemic complications is suggested.

Keywords:acute pancreatitis; rabbits; cytokines; anti-interleukin-8 antibody; acute lunginjury