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

Natalia P. Rocha, Gabriela D. Colpo, Javiera Bravo-Alegria, John A. Lincoln, Jerry S. Wolinsky, John W. Lindsey, Antonio L. Teixeira, Leorah Freeman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)45-48
Number of pages4
JournalJournal of Neuroimmunology
StatePublished - Jan 15 2019
Externally publishedYes


  • Cytokines
  • Endothelin-1
  • Inflammation
  • Multiple sclerosis
  • Th1/Th2 response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology


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