Multi-Organ Inflammatory and Endocrine Crosstalk Shapes the Early Brain Response to Combined Burn and Blast Injury.
4 affiliations
- 1Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA.
- 2Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
- 3Department of Genetics, Harvard University School of Medicine, Cambridge, Massachusetts, USA.
- 4Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abstract
The pathology of concomitant burn and traumatic brain injury remains poorly defined, despite their frequent co-occurrence in military settings and the potential for deleterious synergy. To address this gap, we combined established models of blast-induced mild traumatic brain injury and 15% total body surface area flame burn to approximate a common combat-related trauma and examined how the injuries interact to shape systemic inflammation and brain transcriptional programs. Burn injury induced systemic G-CSF and IL-6 secretion and hematopoietic reprioritization, whereas overlapping brain injury did not substantially alter these systemic effects but magnified brain transcriptional responses relative to single injuries. Bulk RNA-seq profiling at 6 h post-injury revealed enriched gene sets associated with inflammation and endocrine stress in the combined injury group, alongside elevated systemic cytokines and corticosterone; thereby suggesting concurrent immune-endocrine activation. Since our prior work demonstrated burn wound-associated IL-1 signaling induces G-CSF and IL-6 secretion, we tested IL-1 neutralizing antibodies and anakinra as therapies. Treatment reduced G-CSF and IL-6 secretion, improved erythropoiesis, and selectively modulated brain transcriptional changes. Single-nucleus RNA-seq projection mapping predicted that the transcripts altered by combined injury were broadly enriched across vascular and glial cell types. Targeted expression profiling identified a shared brain-liver signature characterized by an IL-1/6-dependent inflammatory response alongside an interleukin-independent stress response. These findings highlight IL-1-responsive inflammatory signals and endocrine stress interactions within a multi-organ network that shapes the early brain transcriptional response to the combined injury.
Related
- Endocrine–Immune Crosstalk in Pediatric Autoimmune Diseases: A Systematic Review of the Role of Micronutrients, with Emphasis on Vitamin D
- Effects of azacitidine combined with venetoclax on inflammatory markers and overall response rate in elderly patients with newly diagnosed acute myeloid leukemia
- β3-Integrin controls pericyte metabolic states and shapes tumour-stromal metabolic crosstalk in breast cancer
- Pexidartinib modulates pro-inflammatory cytokines in a co-culture model of stromal-immune cell crosstalk in tenosynovial giant cell tumor
- A surprising complete radiographic response to palbociclib plus endocrine therapy in an HR-positive, HER2-low lung, pleural, and lymph node metastatic breast cancer patient: a case report.
BibTeX
@article{schwierling2026multiorgan,
title = {{Multi-Organ Inflammatory and Endocrine Crosstalk Shapes the Early Brain Response to Combined Burn and Blast Injury.}},
author = {Hana C Schwierling and Satarupa Sengupta and John G Noel and Christopher J O'Connell and Andrew S Potter and Mike Adam and Matthew J Robson and Jason C Gardner},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2026},
month = oct,
doi = {10.1096/fj.202504681r},
url = {https://europepmc.org/article/MED/42952293},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-Organ Inflammatory and Endocrine Crosstalk Shapes the Early Brain Response to Combined Burn and Blast Injury.
AU - Hana C Schwierling
AU - Satarupa Sengupta
AU - John G Noel
AU - Christopher J O'Connell
AU - Andrew S Potter
AU - Mike Adam
AU - Matthew J Robson
AU - Jason C Gardner
PY - 2026
DA - 2026/10/29
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DO - 10.1096/fj.202504681r
UR - https://europepmc.org/article/MED/42952293
AB - The pathology of concomitant burn and traumatic brain injury remains poorly defined, despite their frequent co-occurrence in military settings and the potential for deleterious synergy. To address this gap, we combined established models of blast-induced mild traumatic brain injury and 15% total body surface area flame burn to approximate a common combat-related trauma and examined how the injuries interact to shape systemic inflammation and brain transcriptional programs. Burn injury induced systemic G-CSF and IL-6 secretion and hematopoietic reprioritization, whereas overlapping brain injury did not substantially alter these systemic effects but magnified brain transcriptional responses relative to single injuries. Bulk RNA-seq profiling at 6 h post-injury revealed enriched gene sets associated with inflammation and endocrine stress in the combined injury group, alongside elevated systemic cytokines and corticosterone; thereby suggesting concurrent immune-endocrine activation. Since our prior work demonstrated burn wound-associated IL-1 signaling induces G-CSF and IL-6 secretion, we tested IL-1 neutralizing antibodies and anakinra as therapies. Treatment reduced G-CSF and IL-6 secretion, improved erythropoiesis, and selectively modulated brain transcriptional changes. Single-nucleus RNA-seq projection mapping predicted that the transcripts altered by combined injury were broadly enriched across vascular and glial cell types. Targeted expression profiling identified a shared brain-liver signature characterized by an IL-1/6-dependent inflammatory response alongside an interleukin-independent stress response. These findings highlight IL-1-responsive inflammatory signals and endocrine stress interactions within a multi-organ network that shapes the early brain transcriptional response to the combined injury.
SN - 0892-6638
SN - 1530-6860
ER -