Perioperative medicine & outcomes
Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial
Authors' conclusion
These findings illuminate the complex epigenetic modulation influencing monocytes' response to surgical stress, shedding light on potential biomarkers for immune dysregulation.
Study context
- Population
- Colorectal surgery patients; monocytes of healthy volunteers in vitroRCT
- Participants
- 100 patients
- Outcome
- Plasma damage-associated molecular patterns (DAMPs) after surgery
Methodological detailssubstudy of a randomised controlled trial, exploratory subgroup proteomic and epigenomic analyses, in vitro experiments
- Substudy of a randomised controlled trial
- Exploratory subgroup proteomic and epigenomic analyses
- In vitro experiments
Main finding
As reported in the abstract
- HMGB1 mean increase, preop to end of surgery
- 235% (95% CI 166 - 305, P < .0001)
- HMGB1 increase, preop to POD1
- 90% (95% CI 63-118, P = .0004)
- HSP70 mean increase, preop to end of surgery
- 12% (95% CI 3-21, not significant)
- HSP70 increase, preop to POD1
- 30% (95% CI 18-41, P < .0001)
- Nuclear deoxyribonucleic acid (nDNA) increase at end of surgery
- 66% (95% CI 40-92, P < .0001)
- nDNA increase on POD1
- 94% (95% CI 60-127, P < .0001)
- Mitochondrial DNA (mtDNA) increase at end of surgery
- 370% (95% CI 225-515, P < .0001)
- mtDNA increase on POD1
- 503% (95% CI 332-673, P < .0001)
Further findings
In vitro cytokine production capacity of monocytes incubated with HSP70
- Tumor necrosis factor (TNF) decrease
- 46% (95% CI 29-64, P < .0001)
- IL-6 decrease
- 22% (95% CI 12-32, P = .0004)
- IL-10 decrease
- 19% (95% CI 12-26, P = .0015)
In vitro cytokine production capacity of monocytes incubated with HMGB1
- TNF decrease
- 34% (95% CI 3-65, P = .0003)
- IL-1β decrease
- 24% (95% CI 16-32, P < .0001)
- IL-10 decrease
- 40% (95% CI 21-58, P = .0009)
Inflammatory proteome and monocyte epigenome (exploratory subgroup)
- Significant changes in gene accessibility, particularly CXCL8 (IL-8), IL-6 and IFN-γ
- IRF enrichment in loci with decreased accessibility; AP-1 motif enrichment in loci with increased accessibility
Original publication
Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial. Anesth Analg. Published 25 October 2024. doi:10.
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