Cytokine-induced modulation of cellular adhesion to human cerebral endothelial cells is mediated by soluble vascular cell adhesion molecule-1

Tumour necrosis factor-alpha (TNF-alpha) has been proposed as one of the ke y mediators of inflammatory diseases of the CNS such as multiple sclerosis, It has been shown to induce the expression of adhesion molecules which is a prerequisite for the transmigration of immune cells through the blood-bra in barrier. We therefore investigated the role of TNF-alpha in the expressi on and release of vascular cell adhesion molecule-1 (VCAM-1) in cultures of human cerebral endothelial. cells (HCEC) in comparison with peripheral blo od mononuclear cells (PBMC). A time- and dose-dependent expression of VCAM- 1 and release of soluble VCAM-1 was detected in HCEC but not PBMC, TNF-alph a-induced release of soluble VCAM-1 was further increased by cotreatment wi th interferon-beta (IFN-beta), while IFN-beta alone did not affect VCAM-1 e xpression or the release of soluble VCAM-1, In addition, we observed that p reincubation of PBMC with soluble VCAM-1 completely blocked their adhesion to HCEC, In conclusion, the proinflammatory effect of TNF-alpha on HCEC, wh ich involves the induction of VCAM-1 expression and cellular adhesion, is f ollowed by the consecutive effects of soluble VCAM-1 release in blocking ad hesion and downregulating further cellular infiltration. Increasing soluble VCAM-1 release during active inflammation could be another mechanism by wh ich IFN-beta treatment exerts protective effects in multiple sclerosis pati ents.