SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS WITH A TNF BINDING-PROTEIN (TNFBP) CORRELATES WITH DOWN-REGULATION OF VCAM-1 VLA-4/

The effect of a novel TNF binding protein (TNFbp), a polyethylene glyc ol-linked form of the type I soluble receptor of TNF, on the expressio n of adhesion molecules has been investigated with a passive transfer model of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice . The expression of L-selectin, VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was examined by FACS analysis. T he expression of VCAM-1 and ICAM-1 was investigated by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals sensitized f or EAE and treated with TNFbp, the expression of VCAM-1 in the central nervous system as well as VLA-4 on spleen cells was clearly diminishe d. Reduction in VCAM-1 staining and VLA-4 expression corresponded to i nhibition of inflammation in the spinal cord and to prevention of clin ical signs of EAE. The results have also shown that myelin basic prote in responses as well as non-antigen-specific responses were not dimini shed in animals treated with TNFbp. The findings suggest that TNFbp mi ght prevent EAE development by modulating the expression of VCAM-1 and VLA-4.