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Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study

Cortisol exerts a broad anti-inflammatory effect on the immune system. Inflammatory cytokines contribute to the molecular signalling pathways implicated in various autoimmune and inflammatory conditions. However, the mechanisms by which cortisol modulates such signalling pathways remain uncertain. L...

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Autores principales: Rajasundaram, Skanda, Rahman, Rezbieara P., Woolf, Benjamin, Zhao, Sizheng Steven, Gill, Dipender
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774857/
https://www.ncbi.nlm.nih.gov/pubmed/35052454
http://dx.doi.org/10.3390/genes13010116
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author Rajasundaram, Skanda
Rahman, Rezbieara P.
Woolf, Benjamin
Zhao, Sizheng Steven
Gill, Dipender
author_facet Rajasundaram, Skanda
Rahman, Rezbieara P.
Woolf, Benjamin
Zhao, Sizheng Steven
Gill, Dipender
author_sort Rajasundaram, Skanda
collection PubMed
description Cortisol exerts a broad anti-inflammatory effect on the immune system. Inflammatory cytokines contribute to the molecular signalling pathways implicated in various autoimmune and inflammatory conditions. However, the mechanisms by which cortisol modulates such signalling pathways remain uncertain. Leveraging summary-level data from the CORtisol NETwork (CORNET, n = 25,314) and FINRISK (n = 8293) genome-wide association studies, we used two-sample Mendelian randomisation to investigate the causal effect of genetically proxied morning cortisol levels on 42 circulating cytokines. We found that increased genetically proxied morning cortisol levels were associated with reduced levels of IL-8 and increased levels of MIF. These results provide mechanistic insight into the immunomodulatory effects of endogenous cortisol and the therapeutic effects of exogenous corticosteroids. Clinically, our findings underline the therapeutic importance of steroids in inflammatory conditions where IL-8 and MIF play a central pathophysiological role in the onset and progression of disease.
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spelling pubmed-87748572022-01-21 Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study Rajasundaram, Skanda Rahman, Rezbieara P. Woolf, Benjamin Zhao, Sizheng Steven Gill, Dipender Genes (Basel) Article Cortisol exerts a broad anti-inflammatory effect on the immune system. Inflammatory cytokines contribute to the molecular signalling pathways implicated in various autoimmune and inflammatory conditions. However, the mechanisms by which cortisol modulates such signalling pathways remain uncertain. Leveraging summary-level data from the CORtisol NETwork (CORNET, n = 25,314) and FINRISK (n = 8293) genome-wide association studies, we used two-sample Mendelian randomisation to investigate the causal effect of genetically proxied morning cortisol levels on 42 circulating cytokines. We found that increased genetically proxied morning cortisol levels were associated with reduced levels of IL-8 and increased levels of MIF. These results provide mechanistic insight into the immunomodulatory effects of endogenous cortisol and the therapeutic effects of exogenous corticosteroids. Clinically, our findings underline the therapeutic importance of steroids in inflammatory conditions where IL-8 and MIF play a central pathophysiological role in the onset and progression of disease. MDPI 2022-01-08 /pmc/articles/PMC8774857/ /pubmed/35052454 http://dx.doi.org/10.3390/genes13010116 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rajasundaram, Skanda
Rahman, Rezbieara P.
Woolf, Benjamin
Zhao, Sizheng Steven
Gill, Dipender
Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title_full Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title_fullStr Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title_full_unstemmed Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title_short Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study
title_sort morning cortisol and circulating inflammatory cytokine levels: a mendelian randomisation study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774857/
https://www.ncbi.nlm.nih.gov/pubmed/35052454
http://dx.doi.org/10.3390/genes13010116
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