The role of cortisol in immunosuppression in subarachnoid haemorrhage
Abstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-023-01222-3 |
| _version_ | 1797577239425974272 |
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| author | Margaret E. Hoadley James Galea Navneet Singh Sharon Hulme David O. Ajao Nancy Rothwell Andrew King Pippa Tyrrell Stephen J. Hopkins |
| author_facet | Margaret E. Hoadley James Galea Navneet Singh Sharon Hulme David O. Ajao Nancy Rothwell Andrew King Pippa Tyrrell Stephen J. Hopkins |
| author_sort | Margaret E. Hoadley |
| collection | DOAJ |
| description | Abstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Results Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. Conclusion These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses. |
| first_indexed | 2024-03-10T22:06:19Z |
| format | Article |
| id | doaj.art-662161bb7a9b41a3a4fbca781712922f |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-10T22:06:19Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-662161bb7a9b41a3a4fbca781712922f2023-11-19T12:47:47ZengBMCEuropean Journal of Medical Research2047-783X2023-08-0128111210.1186/s40001-023-01222-3The role of cortisol in immunosuppression in subarachnoid haemorrhageMargaret E. Hoadley0James Galea1Navneet Singh2Sharon Hulme3David O. Ajao4Nancy Rothwell5Andrew King6Pippa Tyrrell7Stephen J. Hopkins8Northern Care Alliance Research and Innovation, Salford Royal NHS Foundation TrustNinewells Hospital and Medical School, University of DundeeAtkinson Morley, Dept of Neurosurgery, St Georges HospitalDivision of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of ManchesterDivision of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of ManchesterFaculty of Life Sciences, University of ManchesterDivision of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of ManchesterDivision of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of ManchesterNorthern Care Alliance Research and Innovation, Salford Royal NHS Foundation TrustAbstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Results Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. Conclusion These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.https://doi.org/10.1186/s40001-023-01222-3CytokinesImmune responseImmunosuppressionCortisolRU-486Infection |
| spellingShingle | Margaret E. Hoadley James Galea Navneet Singh Sharon Hulme David O. Ajao Nancy Rothwell Andrew King Pippa Tyrrell Stephen J. Hopkins The role of cortisol in immunosuppression in subarachnoid haemorrhage European Journal of Medical Research Cytokines Immune response Immunosuppression Cortisol RU-486 Infection |
| title | The role of cortisol in immunosuppression in subarachnoid haemorrhage |
| title_full | The role of cortisol in immunosuppression in subarachnoid haemorrhage |
| title_fullStr | The role of cortisol in immunosuppression in subarachnoid haemorrhage |
| title_full_unstemmed | The role of cortisol in immunosuppression in subarachnoid haemorrhage |
| title_short | The role of cortisol in immunosuppression in subarachnoid haemorrhage |
| title_sort | role of cortisol in immunosuppression in subarachnoid haemorrhage |
| topic | Cytokines Immune response Immunosuppression Cortisol RU-486 Infection |
| url | https://doi.org/10.1186/s40001-023-01222-3 |
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