Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients after acute surgical trauma

Edward A. Ganio, Natalie Stanley, Viktoria Lindberg-Larsen, Jakob Einhaus, Amy S. Tsai, Franck Verdonk, Anthony Culos, Sajjad Ghaemi, Kristen K. Rumer, Ina A. Stelzer, Dyani Gaudilliere, Eileen Tsai, Ramin Fallahzadeh, Benjamin Choisy, Henrik Kehlet, Nima Aghaeepour, Martin S. Angst and Brice Gaudilliere ()
Additional contact information
Edward A. Ganio: Stanford University
Natalie Stanley: Stanford University
Viktoria Lindberg-Larsen: The Lundbeck Foundation Center for Fast-track Hip and Knee replacement
Jakob Einhaus: Stanford University
Amy S. Tsai: Stanford University
Franck Verdonk: Stanford University
Anthony Culos: Stanford University
Sajjad Ghaemi: Stanford University
Kristen K. Rumer: Stanford University
Ina A. Stelzer: Stanford University
Dyani Gaudilliere: Stanford University
Eileen Tsai: Stanford University
Ramin Fallahzadeh: Stanford University
Benjamin Choisy: Stanford University
Henrik Kehlet: Section of Surgical Pathophysiology 7621, Rigshospitalet
Nima Aghaeepour: Stanford University
Martin S. Angst: Stanford University
Brice Gaudilliere: Stanford University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17565-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17565-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17565-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().