Summary

The transmigration of leukocytes across the endothelium is aprerequisite for the inflammatory process. Leukocyte-endotheliuminteraction is regulated by several endothelial adhesionmolecules, 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, suchas TNFα. In vivo a small part of these adhesion molecules is shedby proteases, and can be detected in the circulation. In thisstudy, the time course of the TNFα-induced accumulation inthe blood of three circulating soluble adhesion molecules,sE-selectin, sICAM-1 and sVCAM-1, was studied in plasmasamples of tumor patients enrolled in a phase I trial receivingTNFα. Two different cohorts were studied. Eleven patients received a continuous 24-hour TNFα infusion while 10 otherpatients received a 5-day continuous TNFa infusion. After24 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 after5 days of continuous TNFα infusion. sVCAM-1 and sICAM-1levels showed an increase during the infusion with a maximumat 3 to 5 days and stayed elevated after discontinuation ofthe TNFα infusion. In contrast, sE-selectin reached its peak atday 1 and declined thereafter. In conclusion, sVCAM-1 andsICAM-1 show a different accumulation pattern upon TNFαinfusion as compared to sE-selectin in man.