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Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy
1Division of Hematology, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA. jharlan@u.washington.edu
Objective:
This review describes efforts to develop therapies directed at leukocyte and endothelial adhesion molecules for the treatment of acute and chronic inflammatory diseases, including hemorrhagic shock.
Data Sources And Study Selection:
Published research and review articles and Web sites relating to the clinical use of drugs directed to leukocyte or endothelial cell adhesion molecules.
Data Extraction And Synthesis:
The results of relevant studies of adhesion blockade are reviewed. Trials in putative clinical ischemia-reperfusion disorders, particularly traumatic shock, are emphasized. Trials are designated as positive or negative, depending on whether the primary end points established by the trial investigators were met.
Conclusions:
Blockade of leukocyte adhesion to endothelium by monoclonal antibodies or other antagonists has been demonstrated to reduce vascular and tissue injury in a wide variety of animal models of inflammatory and immune disease. Anti-adhesion therapy directed at lymphocyte trafficking has shown efficacy in several phase 2 and 3 clinical trials in inflammatory bowel disease, multiple sclerosis, and psoriasis. Despite strong preclinical data, results of phase 2 and 3 trials of neutrophil adhesion blockade in putative ischemia-reperfusion disorders-stroke, myocardial infarction, and hemorrhagic shock-have been disappointing.