Distinct accumulation patterns of soluble forms of E-selectin, VCAM-1 and ICAM-1 upon infusion of TNFα in tumor patients
article
The transmigration of leukocytes across the endothelium is a prerequisite for the inflammatory process. Leukocyte-endothelium interaction is regulated by several endothelial adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Their expression is enhanced by inflammatory mediators, such as TNFα. In vivo a small part of these adhesion molecules is shed by proteases, and can be detected in the circulation. In this study, the time course of the TNFα-induced accumulation in the blood of three circulating soluble adhesion molecules, sE-selectin, sICAM-1 and sVCAM-1, was studied in plasma samples of tumor patients enrolled in a phase 1 trial receiving TNFα. Two different cohorts were studied. Eleven patients received a continuous 24-hour TNFα infusion while 10 other patients received a 5-day continuous TNFα infusion. After 24 hours of TNFα infusion sE-selectin levels increased by 1985 ± 312 %, sVCAM-1 by 301 ± 19 % and sICAM-1 by 445 ± 82 %. Differences in accumulation patterns were observed after 5 days of continuous TNFα infusion. sVCAM-1 and sICAM-1 levels showed an increase during the infusion with a maximum at 3 to 5 days and stayed elevated after discontinuation of the TNFα infusion. In contrast, sE-selectin reached its peak at day 1 and declined thereafter. In conclusion, sVCAM-1 and sICAM-1 show a different accumulation pattern upon TNFα infusion as compared to sE-selectin in man.
Topics
Biomedical ResearchCell adhesion moleculeEndotheliumInflammatory mediatorLeukocyte adhesionSoluble receptorTumor necrosis factorantineoplastic agentcell adhesion moleculeendothelial leukocyte adhesion molecule 1intercellular adhesion molecule 1tumor necrosis factor alphavascular cell adhesion molecule 1blood samplingbreast cancercancercancer chemotherapycancer radiotherapycarcinoidclinical articleclinical trialcohort analysiscolon cancercontinuous infusioncontrolled clinical trialcontrolled studydrug dose regimendrug effectdrug withdrawalHodgkin diseasekidney cancerlung cancermelanomapancreas cancerphase 1 clinical trialprotein aggregationprotein blood levelsarcomaAdultAgedBiological MarkersCell Adhesion MoleculesClinical Trials, Phase ICohort StudiesE-SelectinEndothelium, VascularHumansIntercellular Adhesion Molecule-1KineticsMiddle AgedNeoplasmsSolubilityTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1
TNO Identifier
237134
ISSN
03406245
Source
Thrombosis and Haemostasis, 89(6), pp. 1052-1057.
Pages
1052-1057
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