Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis.

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Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis.

J Neuroimmunol. 2018 Nov 15;326:45-48

Authors: Rocha NP, Colpo GD, Bravo-Alegria J, Lincoln JA, Wolinsky JS, Lindsey JW, Teixeira AL, Freeman L

Abstract
BACKGROUND: Identifying pathways linking neuroinflammation and neurodegeneration is essential to help prevent disability progression in people with multiple sclerosis (MS). Endothelin-1 (ET-1) is a potent vasoconstrictor thought to contribute to cerebral hypoperfusion and tissue damage in MS. Its link with the neuroinflammatory process remains poorly investigated.
OBJECTIVES: To determine plasma ET-1 levels in treatment-naïve people with MS and controls, and the relationship between ET-1 and other peripheral immune mediator levels as potential markers of the disease process.
METHODS: This is a retrospective study that included specimens previously collected from 35 treatment-naïve patients with clinically isolated syndrome highly suggestive of MS or definite MS and 35 sex- and age-matched controls. ET-1 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA), and plasma cytokine levels [interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] were simultaneously measured by Multiplex assay.
RESULTS: ET-1 levels were significantly increased in MS patients compared to controls. No significant difference in cytokine levels between the groups were found. However, a significant increase in IFN-γ/IL-4 ratio was observed in patients with MS in comparison with controls, suggestive of Th1 skewed response. Binary logistic regression was performed to ascertain the effects of age, sex, ET-1 and cytokine levels on the likelihood of MS diagnosis. In the final model, ET-1, IL-4 and IFN-γ levels remained as predictors of MS. There was no significant correlation between ET-1 and cytokine levels.
CONCLUSIONS: Patients with MS presented increased levels of ET-1 and an immune response biased towards a Th1 profile. Although both ET-1 and Th1 cytokine profile were predictors of MS diagnosis, ET-1 levels were not associated with peripheral immune markers, suggesting that these changes may occur independently.

PMID: 30472305 [PubMed - as supplied by publisher]

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