Efficacy of antibodies to adhesion molecules, CD11a or CD18, in rabbit models of uveitis.
Adhesion molecules play a critical role in leukocyte emigration to a site of inflammation. In order to assess the potential therapeutic benefit of blocking adhesion molecule function in anterior uveitis, the efficacy of antibodies to specific adhesion molecules was tested in 3 separate rabbit models of anterior uveitis. Antibodies to two different leukocyte molecules, CD11a and CD18, and antibodies to the endothelial ligand for CD11a/CD18, ICAM-1 (intercellular adhesion molecule-1, CD54), were studied in inflammation after intravitreally injected interleukin-1, intravitreally injected endotoxin, or an ocular reversed passive Arthus reaction. The CD18 antibody (2 mg/kg intravenously) reduced the cellular infiltrate with each of these 3 models. The antibody to CD11a was equally effective but was tested only in the IL-1-induced model. The antibody to ICAM-1 reduced the cellular infiltrate associated with this model, but the results did not reach statistical significance. None of the antibodies was able to reduce the associated increase in vascular permeability as measured by protein in the aqueous humor. The antibody to CD18 failed to reduce the inflammation if it was administered 24 hours after the intravitreally injected endotoxin. These observations demonstrate that leukocyte migration into the anterior segment of the eye is dependent on the CD11a/CD18 complex.
Rosenbaum
J T
JT
Oregon Health Sciences University, Casey Eye Institute, Portland 97201.
Boney
R S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004731:Endotoxins; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D007074:Immunoglobulin G; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1; C044101:endotoxin, Escherichia coli