Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: Correlation with magnetic resonance imaging

Abstract

Adhesion molecules are important in T-cell trafficking to sites of inflammation. We determined levels of circulating vascular cell adhesion molecule-1 (VCAM-1), L-selectin, and E-selectin in the serum of 147 patients with definite multiple sclerosis of the remitting-relapsing or secondary progressive type. Soluble VCAM-1 and L-selectin concentrations were increased compared to levels in a large group of control subjects. 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 levels of soluble tumor necrosis factor receptor (60 kd) were also raised (2.64 +/- 1.23 vs 2.17 +/- 0.69 ng/ml in subjects with other neurological 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 concentrations of soluble tumor necrosis factor receptor. In 13 patients with viral encephalitis, similar observations were made. Raised levels of soluble VCAM-1 and L-selectin probably reflect cytokine-induced endothelial cell and T-lymphocyte/monocyte activation occurring in the process of T-cell migration into the central nervous system. Tumor necrosis factor-alpha may be critically involved.

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

“…CSF levels of sICAM-1 and sTNFα were positively correlated in patients with acute relapsing MS during an exacerbation 11 . This is in light of previous evidence indicating that proinflammatory cytokines such as TNFα and adhesion molecules (sICAM-1) may represent markers of inflammation 3,4,11 .…”

“…In this sense, high concentrations of sICAM-1 and VCAM-1 in the peripheral blood during active disease would reflect BBB damage and may further serve as an adhesion ligand during extravasation of activated leukocytes into the brain tissue 24,27 . Indeed the extent of ICAM-1 activation may vary within different regions of the inflamed brain tissue which ultimately may account for the varying degrees of neurological deficit 2,4,28,29 .…”

“…tic histological features of the disease include perivenular leukocyte infiltration with multifocal inflammation accompanied by primary demyelination with relative but not absolute axonal sparing 4 . The inflammatory lesion develops in a multistep process initiated by transmigration of CNS antigen-specific autoreactive effector cells across the endothelial blood brain barrier (BBB).…”

A Pilot, Open Label, Clinical Trial Using Hydroxyzine in Multiple Sclerosis

“…Mast cells are also a rich source of most known cytokines including TNF-a and could release it upon immunologic stimulation (30). TNF-a (31) and soluble TNF receptor (31) were detected in CSF of MS patients and could participate in BBB impairment (32). The unique mast cell protease tryptase was also increased in the CSF of MS patients (17).…”

Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress

“…The vasodilatory and proinflammatory TNF-␣ (Galli, 1993) could also be involved since this cytokine is released along with histamine from rat hypothalamic mast cells and has been shown to regulate BBB permeability (Kim et al, 1992). In fact, TNF-␣ was reported to be increased in the cerebrospinal fluid of MS patients (Hartung et al, 1995), and interference with TNF function prevents encephalomyelitis (EAE) (Klinkert et al, 1997).…”