Natalizumab treatment reduces endothelial activity in MS patients.

Vascular cell adhesion molecule-1 a ligand for leukocyte very late activating antigen-4 is a key player in leukocyte extravasation in MS lesions. Natalizumab a monoclonal antibody against VLA-4 blocks this interaction. VCAM-1 and its soluble form are up-regulated during endothelial activation in MS. We investigated the effect of Natalizumab on sVCAM-1 and VLA-4 on circulating leukocytes in MS patients. Natalizumab reduced levels of sVCAM-1 compared to controls (256 vs. 597 ng/mL). This effect was sustained and only reversed in patients with neutralizing antibodies against Natalizumab. Correspondingly Natalizumab diminished VLA-4 on leukocyte subsets. Our findings indicate that Natalizumab reduces transmigration not only by blocking VLA-4 but also by down-regulating VCAM-1.