Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients after acute surgical trauma.
Acute Disease
Adaptive Immunity
/ drug effects
Aged
Arthroplasty, Replacement, Hip
/ adverse effects
Case-Control Studies
Double-Blind Method
Fatigue
/ drug therapy
Female
Glucocorticoids
/ pharmacology
Humans
Male
Methylprednisolone
/ pharmacology
NF-KappaB Inhibitor alpha
/ metabolism
Pain
/ drug therapy
Phenotype
Phosphorylation
STAT3 Transcription Factor
/ metabolism
Treatment Outcome
Wounds and Injuries
/ etiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 07 2020
27 07 2020
Historique:
received:
21
10
2019
accepted:
03
07
2020
entrez:
29
7
2020
pubmed:
29
7
2020
medline:
9
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32719355
doi: 10.1038/s41467-020-17565-y
pii: 10.1038/s41467-020-17565-y
pmc: PMC7385146
doi:
Substances chimiques
Glucocorticoids
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
NF-KappaB Inhibitor alpha
139874-52-5
Methylprednisolone
X4W7ZR7023
Banques de données
ClinicalTrials.gov
['NCT02542592']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3737Subventions
Organisme : NIGMS NIH HHS
ID : K23 GM111657
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR003143
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM137936
Pays : United States
Organisme : NINDS NIH HHS
ID : R61 NS114926
Pays : United States
Commentaires et corrections
Type : ErratumIn
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