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, J W Lindsey, Antonio L. Teixeira, Leorah Freeman

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages45-48
Number of pages4
JournalJournal of Neuroimmunology
Volume326
DOIs
StatePublished - Jan 15 2019

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Endothelin-1
Multiple Sclerosis
Inflammation
Cytokines
Interleukin-4
Interferon-gamma
Interleukin-13
Interleukin-5
Vasoconstrictor Agents
Interleukin-12
Interleukin-1beta
Interleukin-10
Interleukin-2
Interleukin-6
Retrospective Studies
Tumor Necrosis Factor-alpha
Biomarkers
Logistic Models
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Rocha, N. P., Colpo, G. D., Bravo-Alegria, J., Lincoln, J. A., Wolinsky, J. S., Lindsey, J. W., ... Freeman, L. (2019). Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis. Journal of Neuroimmunology, 326, 45-48. https://doi.org/10.1016/j.jneuroim.2018.11.007

Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis. / Rocha, Natalia P.; Colpo, Gabriela D.; Bravo-Alegria, Javiera; Lincoln, John A; Wolinsky, Jerry S.; Lindsey, J W; Teixeira, Antonio L.; Freeman, Leorah.

In: Journal of Neuroimmunology, Vol. 326, 15.01.2019, p. 45-48.

Research output: Contribution to journalArticle

Rocha, NP, Colpo, GD, Bravo-Alegria, J, Lincoln, JA, Wolinsky, JS, Lindsey, JW, Teixeira, AL & Freeman, L 2019, 'Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis', Journal of Neuroimmunology, vol. 326, pp. 45-48. https://doi.org/10.1016/j.jneuroim.2018.11.007
Rocha, Natalia P. ; Colpo, Gabriela D. ; Bravo-Alegria, Javiera ; Lincoln, John A ; Wolinsky, Jerry S. ; Lindsey, J W ; Teixeira, Antonio L. ; Freeman, Leorah. / Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis. In: Journal of Neuroimmunology. 2019 ; Vol. 326. pp. 45-48.
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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-na{\"i}ve 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-na{\"i}ve 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.",
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AU - Lincoln, John A

AU - Wolinsky, Jerry S.

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AU - Teixeira, Antonio L.

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AB - 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.

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