Attenuation of the Inflammatory Response in an Animal Colitis Model by Neutrophil Inhibitory Factor, a Novel β₂-Integrin Antagonist

Abstract

Background: Neutrophils are significant effector cells in acute inflammatory bowel disease. Recruitment of these cells is dependent on β₂-integrin-mediated adhesion and transmigration. The efficacy of neutrophil inhibitory factor (NIF), an antagonist of the β₂-integrin CD11b/CD18, in ameliorating inflammation was tested in an animal model of acute colitis. Method: 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). Conclusion: 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.

Key Words:

• Adhesion
• colitis
• eicosanoids
• integrin