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


OBJECTIVE
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.


CONCLUSIONS
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.
Osman
M O
MO
Department of Surgery L, Aarhus University Hospital, Denmark.
Kristensen
J U
JU
Jacobsen
N O
NO
Lausten
S B
SB
Deleuran
B
B
Deleuran
M
M
Gesser
B
B
Matsushima
K
K
Larsen
C G
CG
Jensen
S L
SL
D000681:Amylases / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D001202:Ascitic Fluid / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000097:blood; D005260:Female; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000276:immunology*; D008049:Lipase / Q000097:blood; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001786:Blood Glucose; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D008049:Lipase; D000681:Amylases; D002118:Calcium