Key result
Subarachnoid haemorrhage is linked to ~94% lower LPS-induced TNF-α production, an immunosuppressive effect reversed by RU-486.
Why the study?
The study sought to determine whether cortisol suppresses innate and T cell-mediated cytokine production and could be involved in reducing peripheral cytokine production after subarachnoid haemorrhage.
Does the cortisol antagonist mifepristone (RU-486) reverse cortisol-induced suppression of innate and T cell-mediated cytokine production in whole blood from patients with subarachnoid haemorrhage?
Observational (n=83)
No
Does the cortisol antagonist mifepristone (RU-486) reverse cortisol-induced suppression of innate and T cell-mediated cytokine production in whole blood from patients with subarachnoid haemorrhage?
Effect estimate: 94% reduction
p-value: p=<0.0001
Cortisol suppresses early innate immune responses following subarachnoid haemorrhage, and this suppression can be partially reversed ex vivo by the glucocorticoid antagonist mifepristone.
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.
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Hoadley et al. (2023) conducted an observational in Subarachnoid haemorrhage (n=83). Subarachnoid haemorrhage (SAH) vs. Healthy controls was evaluated on LPS-induced TNF-α production (94% reduction, p=<0.0001). Subarachnoid haemorrhage was associated with a 94% reduction in LPS-induced TNF-α production compared to healthy controls, an immunosuppressive effect that was reversed ex vivo by the cortisol antagonist RU-486.
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