CIRCULATING ADHESION MOLECULES AND TUMOR-NECROSIS-FACTOR RECEPTOR IN MULTIPLE-SCLEROSIS - CORRELATION WITH MAGNETIC-RESONANCE-IMAGING

Adhesion molecules are important in T-cell trafficking to sites of inf lammation. We determined levels of circulating vascular cell adhesion molecule-1(VCAM-1), L-selectin, and E-selectin in the serum of 147 pat ients with definite multiple sclerosis of the remitting-relapsing or s econdary progressive type. Soluble VCAM-1 and L-selectin concentration s were increased compared to levels in a large group of control subjec ts. Levels were highest in patients with gadolinium-enhancing lesions on magnetic resonance imaging (VCAM-1: 1,011 +/- 276 vs 626 +/- 87 ng/ ml; L-selectin: 1,130 +/- 272 vs 793 +/- 207 ng/ml [mean +/- standard deviation]; p < 0.0001 vs patients without enhancing lesions). Serum l evels of soluble tumor necrosis factor receptor (60 kd) were also rais ed (2.64 +/- 1.23 vs 2.17 +/- 0.69 ng/ml in subjects with other neurol ogical diseases and 2.1 +/- 0.77 ng/ml in healthy control subjects; p < 0.05). Soluble VCAM-1 and L-selectin levels were correlated to conce ntrations of soluble tumor necrosis factor receptor. In 13 patients wi th viral encephalitis, similar observations were made. Raised levels o f soluble VCAM-1 and L-selectin probably reflect cytokine-induced endo thelial cell and T-lymphocyte/monocyte activation occurring in the pro cess of T-cell migration into the central nervous system. Tumor necros is factor-alpha may be critically involved.