T lymphocytes conditioned with Interferon beta induce membrane and solubleVCAM on human brain endothelial cells

Vascular cell adhesion molecule (VCAM)-1 plays a critical role in mediating inflammatory cell adhesion and migration. Factors regulating the expressio n of membrane (m)VCAM and its cleaved counterpart soluble (s)VCAM are poorl y understood. We previously demonstrated that serum sVCAM levels are increa sed in multiple sclerosis (MS) patients treated with interferon beta 1b (IF N beta 1b), which correlated with a reduction in gadolinium enhancing lesio ns on magnetic resonance imaging. However, subsequent studies have shown th at IFN beta does not directly induce VCAM expression on endothelial cells. We demonstrate here that co-culture with IFN beta -conditioned T cells indu ces mVCAM on human brain endothelial cells (HBEC). Further, rapid shedding of sVCAM occurs, which mirrors the response after in vivo IFN beta treatmen t. The VCAM induction is mediated partially through tumor necrosis factor ( TNF)alpha and can be abrogated by sTNF receptor. VCAM could also be induced on astroglioma lines using IFN beta -conditioned T cells, which suggests t he effect is not specific for HBEC. Kinetic studies demonstrated an increas e in the sVCAM to mVCAM ratio over time, which may contribute to the ultima te therapeutic effect of IFN beta in patients. These data have important im plications for understanding the events occurring at the blood brain barrie r in vivo, and for determining the mechanism of action of IFN beta in MS. ( C) 2001 Elsevier Science B.V. All rights reserved.