Attenuation of the inflammatory response in an animal colitis model by neutrophil inhibitory factor, a novel beta 2-integrin antagonist.
BACKGROUND
Neutrophils are significant effector cells in acute inflammatory bowel disease. Recruitment of these cells is dependent on beta 2-integrin-mediated adhesion and transmigration. The efficacy of neutrophil inhibitory factor (NIF), an antagonist of the beta 2-integrin CD11b/CD18, in ameliorating inflammation was tested in an animal model of acute colitis.


METHODS
Immune-complex colitis was induced in groups of rabbits by using various formalin concentrations (2%, 0.75%, and 0.5%). Animals were treated with rNIF, 10 mg/kg. After they had been killed the mucosal appearance was scored, and tissue saved for histology and quantitation of myeloperoxidase (MPO), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2).


RESULTS
In the 2% formalin group therapy with rNIF resulted in lower LTB4 (p < 0.05) levels. For the 0.75% and 0.5% groups, MPO was lower with rNIF treatment (p < 0.03 and p < 0.05, respectively), as were LTB4 concentrations (both, p < 0.04). PGE2 and TXB2 levels remained unchanged. Histology showed polymorphonuclear cell infiltration to be reduced by rNIF in the 2% and 0.75% formalin-treatment groups (p < 0.05).


CONCLUSIONS
These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.
Meenan
J
J
Dept. of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
Hommes
D W
DW
Mevissen
M
M
Dijkhuizen
S
S
Soule
H
H
Moyle
M
M
Büller
H R
HR
ten Kate
F W
FW
Tytgat
G N
GN
van Deventer
S J
SJ
D000208:Acute Disease; D000818:Animals; D018821:CD18 Antigens; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D005557:Formaldehyde; D006023:Glycoproteins / Q000494:pharmacology*; D015801:Helminth Proteins / Q000494:pharmacology*; D016023:Integrins / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D018821:CD18 Antigens; D015777:Eicosanoids; D006023:Glycoproteins; D015801:Helminth Proteins; D016023:Integrins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C086581:NIF protein, Ancylostoma caninum; D005557:Formaldehyde; D009195:Peroxidase