Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F25%3A10499240" target="_blank" >RIV/00216208:11140/25:10499240 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00141737

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KTXxktGxy6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KTXxktGxy6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12967-025-06652-7" target="_blank" >10.1186/s12967-025-06652-7</a>

Result language

angličtina

Original language name

Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution

Original language description

BACKGROUND: Timely 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. METHODS: We 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. RESULTS: Transcriptomics 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. CONCLUSIONS: We 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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Translational Medicine

ISSN

1479-5876

e-ISSN

1479-5876

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

22

Pages from-to

728

UT code for WoS article

001522052500004

EID of the result in the Scopus database

2-s2.0-105010002769