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

• Published in: Journal of neuroimmunology 2019-01, Vol.326, p.45-48
• Main Authors: Rocha, Natalia P., Colpo, Gabriela D., Bravo-Alegria, Javiera, Lincoln, John A., Wolinsky, Jerry S., Lindsey, John W., Teixeira, Antonio L., Freeman, Leorah
• Format: Article
• Language: English
• Subjects: Cytokines; Endothelin-1; Inflammation; Multiple sclerosis; Th1/Th2 response
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2018.11.007

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. 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. 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. 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. 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. [Display omitted] •ET-1 levels are significantly increased in MS patients compared to controls.•Patients with MS present higher IFN-γ/IL-4 (Th1/Th2) ratio than controls.•ET-1 and Th1 profile are predictors of MS diagnosis in a multivariate analysis.•ET-1 levels are not associated with peripheral cytokines levels.