Therapeutic intervention in inflammatory diseases: a time and place for anti-adhesion therapy.
The recruitment of leukocytes from the blood into tissue is central to the development and maintenance of the majority of inflammatory diseases. This multistep process requires a series of leukocyte-endothelial adhesive interactions, involving several families of adhesion molecules. Molecules that block these interactions have been targeted as potential therapeutic treatments for acute and chronic inflammatory diseases. However, many of the anti-adhesion therapy clinical trials have yielded disappointing outcomes. This review discusses some of the animal models that raise questions about the suitability of anti-adhesion therapy to treat certain inflammatory diseases. The authors suggest that it is crucial to understand the underlying mechanisms and time lines of leukocyte recruitment in each affected tissue and inflammatory disease to develop more effective anti-adhesion therapy.
Norman
M Ursula
MU
Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Kubes
Paul
P
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D016023:Integrins / Q000037:antagonists & inhibitors; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology
D016023:Integrins