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

摘要

Background—Interleukin 8 (IL-8) hasrecently been proposed to have an important role in mediating thedevelopment of the systemic sequelae associated with severe acute pancreatitis. 
Aims—To define the role of IL-8 inacute pancreatitis by neutralising its effects with a monoclonalanti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis. 
Methods—Acute pancreatitis wasinduced by retrograde injection of 5% chenodeoxycholic acid into thepancreatic duct and duct ligation. Twenty rabbits were divided equallyinto two groups: acute pancreatitis controls received physiologicalsaline and the treated group received WS-4, 30 minutes before inductionof acute pancreatitis. 
Results—Pretreatment of animalswith WS-4 resulted in significant down regulation of serum IL-8 andtumour necrosis factor α (TNF-α) from three to six hours afterinduction 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 significantreduction in the CD11b and CD18 positive cells and the amount ofinterstitial neutrophil infiltration in the lungs from WS-4 treatedanimals was seen. In contrast, WS-4 did not alter the amount ofpancreatic 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.