Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients a with multinle sclerosis

Abstract

We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.

Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis

“…Therefore, an increase in sVCAM during IFNbeta treatment could directly result in reduction of immune cell trafficking across the blood brain barrier, which is reflected by diminishing Gd+ lesions. As raised levels of sVCAM and soluble TNF receptors have been demonstrated during relapses [12,17,20] and positive correlations were found with Gd+ lesions [9,21] in cross-sectional studies as well as in the placebo group of this study, naturally occurring fluctuations may rather reflect an endogenous regulatory mechanism to reduce inflammatory activity than disease activity itself. Indeed, the prolonged increase in sVCAM serum levels induced by IFN beta treatment may account for a long lasting immunomodulatory effect leading to an overall suppression of disease activity.…”

ICAM-1 gene is not associated with multiple sclerosis in sardinian patients

“…In conclusion, our data suggest that the increased expression of the ICAM-1 molecule observed in both blood [11,13] and periplaque microvessels [17,20] may be considered an epiphenomenon of the inflammatory process rather than the result of genetic variation. However, other polymorphisms of the ICAM-1 gene need to be explored to definitively exclude this gene as a factor in genetic predisposition to MS. …”

“…The participation of the ICAM-1 molecule has been reported in various inflammatory processes, including multiple sclerosis (MS). Increased expression of ICAM-1 has been found in the blood of actively relapsing MS patients [11,13] and in vessels of MS brain lesions [17,20]. Despite this it is difficult to determine whether this increased expression is partially causative of the MS process or is merely an epiphenomenon of the inflammatory-immunological reaction.…”

Interferon-� 1b leads to a short-term increase of soluble but long-term stabilisation of cell surface bound adhesion molecules in multiple sclerosis

“…Furthermore, the changes in the relatively small number of CNS-specific leukocytes might be diluted by fluctuations in the entire leukocyte population of the peripheral blood. The interand intra-individual variability in consumption with the design of our study might be the reason that we could not find sVCAM-1 and sICAM-1 level changes at the time of clinical relapses or MRI activity that have been described in earlier studies [17,35,36].As we focused on investigating long-term effects of IFN-β we chose relatively long intervals between the investigation points to minimize the error by short-term fluctuations. This interval of 3 month might have been too long to obtain the changes in AM levels during phases of clinical and neuroradiologically determined disease activity.…”