Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients after acute surgical trauma.
Nat Commun
; 11(1): 3737, 2020 07 27.
Article
en En
| MEDLINE
| ID: mdl-32719355
ABSTRACT
Glucocorticoids (GC) are a controversial yet commonly used intervention in the clinical management of acute inflammatory conditions, including sepsis or traumatic injury. In the context of major trauma such as surgery, concerns have been raised regarding adverse effects from GC, thereby necessitating a better understanding of how GCs modulate the immune response. Here we report the results of a randomized controlled trial (NCT02542592) in which we employ a high-dimensional mass cytometry approach to characterize innate and adaptive cell signaling dynamics after a major surgery (primary outcome) in patients treated with placebo or methylprednisolone (MP). A robust, unsupervised bootstrap clustering of immune cell subsets coupled with random forest analysis shows profound (AUC = 0.92, p-value = 3.16E-8) MP-induced alterations of immune cell signaling trajectories, particularly in the adaptive compartments. By contrast, key innate signaling responses previously associated with pain and functional recovery after surgery, including STAT3 and CREB phosphorylation, are not affected by MP. These results imply cell-specific and pathway-specific effects of GCs, and also prompt future studies to examine GCs' effects on clinical outcomes likely dependent on functional adaptive immune responses.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Heridas y Lesiones
/
Artroplastia de Reemplazo de Cadera
/
Inmunidad Adaptativa
/
Glucocorticoides
Tipo de estudio:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos