ArticleJournal of translational medicine2025
Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Causal links between multi-domain risk factors and intervertebral disc degeneration: a systematic review and meta-analysis of Mendelian randomization studies.BMC musculoskeletal disorders · 2026Pooled it
- Article
- Searching for New Possible Peripheral Biomarkers of Cognitive Decline in Down Syndrome: The Role of IL-18 Pathway and its Interaction with TGF-β1 and TNF-α.Neuromolecular medicine · 2026Observational
- The interplay between recovery and immunity in infectious and non-communicable diseases.Frontiers in cellular and infection microbiology · 2026Review
- Genetic variation at the IL-18-137C>G is associated with poor sepsis prognosis and enhanced inflammatory responses: a multicenter hospital-based study.Frontiers in genetics · 2026Article
- The Interleukin Network in Sepsis: From Cytokine Storm to Clinical Applications.Diagnostics (Basel, Switzerland) · 2025Review
- Necroptotic and Apoptotic Pathways in Sepsis: A Comparative Analysis of Pediatric and Adult ICU Patients.Biomedicines · 2025Article
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Authors and funding
20 authors.
Funding
Abstract
backgroundTimely resolution of innate immune responses activated by surgical intervention is crucial for patient recovery. While cytokines and innate immune cells are critical in inflammation resolution, the specific role of IL-18 in these processes remains controversial and underexplored.
methodsWe investigate determinants of successful recovery using peripheral blood samples from orthopedic surgery (ORT) patients (n = 33) at T0 (before surgery), T1 (24 h after surgery) and T2 (3 days after surgery). Monocytes from ORT patients underwent immunophenotyping together with bulk transcriptomic analysis. We found that IL-18 strongly defines the recovery immune signature. These results were further validated in vitro by comparing IL-18 and TNF-α effects on monocytes, and in 3D human intestine organoids together with single cell (sc)-RNAseq analysis.
resultsTranscriptomics of ORT monocytes revealed upregulation of ITG family integrins, namely ITGB3 and ITGB5, CXCL family chemokines, notably CXCL1-3, CXCL5, and SCL/TAL1 factor controlling differentiation and migration, but not pro-inflammatory genes. Similar changes were observed in IL-18 stimulated healthy donor monocytes in vitro, including an increase in CD11b, CD64, and CD86 levels, accompanied by increased phosphorylation of Akt but not NFκB. These changes were attenuated in the presence of TNF-α, thus showing a unique role of IL-18 when acting alone without its most frequent paired cytokine TNF-α. We further confirmed that IL-18 induces monocyte-macrophage transition and migration using human intestinal organoids. Finally, TNF-α/IL-18 ratio showed a high predictive value of clinical severity in septic patients.
conclusionsWe propose a novel role of IL-18 on monocyte migration and macrophage transition characterizing successful orthopedic surgery recovery, as well as the ratio of IL-18/TNF-α as a novel marker of inflammation resolution, with potential implications for patient monitoring and therapeutic strategies.
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