Central role for neurally dysregulated IL-17A in dynamic networks of systemic and local inflammation in combat casualties.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 04 2023
Historique:
received: 06 09 2022
accepted: 15 04 2023
medline: 26 4 2023
pubmed: 25 4 2023
entrez: 24 04 2023
Statut: epublish

Résumé

Dynamic Network Analysis (DyNA) and Dynamic Hypergraphs (DyHyp) were used to define protein-level inflammatory networks at the local (wound effluent) and systemic circulation (serum) levels from 140 active-duty, injured service members (59 with TBI and 81 non-TBI). Interleukin (IL)-17A was the only biomarker elevated significantly in both serum and effluent in TBI vs. non-TBI casualties, and the mediator with the most DyNA connections in TBI wounds. DyNA combining serum and effluent data to define cross-compartment correlations suggested that IL-17A bridges local and systemic circulation at late time points. DyHyp suggested that systemic IL-17A upregulation in TBI patients was associated with tumor necrosis factor-α, while IL-17A downregulation in non-TBI patients was associated with interferon-γ. Correlation analysis suggested differential upregulation of pathogenic Th17 cells, non-pathogenic Th17 cells, and memory/effector T cells. This was associated with reduced procalcitonin in both effluent and serum of TBI patients, in support of an antibacterial effect of Th17 cells in TBI patients. Dysregulation of Th17 responses following TBI may drive cross-compartment inflammation following combat injury, counteracting wound infection at the cost of elevated systemic inflammation.

Identifiants

pubmed: 37095162
doi: 10.1038/s41598-023-33623-z
pii: 10.1038/s41598-023-33623-z
pmc: PMC10126120
doi:

Substances chimiques

Interleukin-17 0
Tumor Necrosis Factor-alpha 0
Interferon-gamma 82115-62-6
Biomarkers 0

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

6618

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ruben Zamora (R)

Department of Surgery, University of Pittsburgh, W944 Starzl Biomedical Sciences Tower, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, 15219, USA.
Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Jonathan A Forsberg (JA)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.

Ashti M Shah (AM)

Department of Surgery, University of Pittsburgh, W944 Starzl Biomedical Sciences Tower, 200 Lothrop St., Pittsburgh, PA, 15213, USA.

Desiree Unselt (D)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.
The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Scott Grey (S)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.
The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Felipe A Lisboa (FA)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.
The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Timothy R Billiar (TR)

Department of Surgery, University of Pittsburgh, W944 Starzl Biomedical Sciences Tower, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, 15219, USA.
Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Seth A Schobel (SA)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.
The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Benjamin K Potter (BK)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.

Eric A Elster (EA)

Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
Surgical Critical Care Initiative (SC2i), Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA.

Yoram Vodovotz (Y)

Department of Surgery, University of Pittsburgh, W944 Starzl Biomedical Sciences Tower, 200 Lothrop St., Pittsburgh, PA, 15213, USA. vodovotzy@upmc.edu.
Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, 15219, USA. vodovotzy@upmc.edu.
Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA. vodovotzy@upmc.edu.

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