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

J 2025

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

PAPATHEODOROU, Ioanna; Gabriela BLAZKOVA; Veronika BOSÁKOVÁ; Zuzana TOMÁŠIKOVÁ; Erin Rose SPEARING et al.

Základní údaje

Originální název

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

Autoři

Vydání

Journal of Translational Medicine, London, BMC, 2025, 1479-5876

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30221 Critical care medicine and Emergency medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.500 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00141755

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

IL-18; Inflammation resolution; Monocyte macrophage transition; Sepsis; Recovery; Cytokine profiling

Štítky

14110114, 14110122, 14110123, 14110132, 14110233, 14110513, 14314010

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 1. 2026 15:16, Mgr. Eva Suchánková

Anotace

V originále

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-alpha 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 NF kappa B. These changes were attenuated in the presence of TNF-alpha, thus showing a unique role of IL-18 when acting alone without its most frequent paired cytokine TNF-alpha. We further confirmed that IL-18 induces monocyte-macrophage transition and migration using human intestinal organoids. Finally, TNF-alpha/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-alpha as a novel marker of inflammation resolution, with potential implications for patient monitoring and therapeutic strategies.

Návaznosti

MUNI/A/1760/2024, interní kód MU

Název: Biomedicínské vědy V

Investor: Masarykova univerzita, Biomedicínské vědy V

NU21-06-00408, projekt VaV

Název: Prediktivní potenciál dynamických změn v subpopulacích neutrofilů a monocytů ve vývoji SIRS a sepse po operaci nebo traumatu.

Investor: Ministerstvo zdravotnictví ČR, Prediktivní potenciál dynamických změn v subpopulacích neutrofilů a monocytů ve vývoji SIRS a sepse po operaci nebo traumatu., Podprogram 1 - standardní

Citovat

PAPATHEODOROU, Ioanna; Gabriela BLAZKOVA; Veronika BOSÁKOVÁ; Zuzana TOMÁŠIKOVÁ; Erin Rose SPEARING; Robin KLIEBER; Pavel OSTASOV; Julie ŠTÍCHOVÁ; Martina DVONČOVÁ; Alexandra MÝTNIKOVÁ; Jan EMMER; Kamila BENDÍČKOVÁ; Tomáš TOMÁŠ; Vladimír ŠRÁMEK; Petros KOLOVOS; Monika HOLUBOVA; Martin HELÁN; Marcela VLKOVÁ; Jan FRIČ a Marcela HORTOVÁ KOHOUTKOVÁ. Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution. Journal of Translational Medicine. London: BMC, 2025, roč. 23, č. 1, s. 1-22. ISSN 1479-5876. Dostupné z: https://doi.org/10.1186/s12967-025-06652-7.

@article{2511403,
   author = {Papatheodorou, Ioanna and Blazkova, Gabriela and Bosáková, Veronika and Tomášiková, Zuzana and Spearing, Erin Rose and Klieber, Robin and Ostasov, Pavel and Štíchová, Julie and Dvončová, Martina and Mýtniková, Alexandra and Emmer, Jan and Bendíčková, Kamila and Tomáš, Tomáš and Šrámek, Vladimír and Kolovos, Petros and Holubova, Monika and Helán, Martin and Vlková, Marcela and Frič, Jan and Hortová Kohoutková, Marcela},
   article_location = {London},
   article_number = {1},
   doi = {https://doi.org/10.1186/s12967-025-06652-7},
   keywords = {IL-18; Inflammation resolution; Monocyte macrophage transition; Sepsis; Recovery; Cytokine profiling},
   language = {eng},
   issn = {1479-5876},
   journal = {Journal of Translational Medicine},
   title = {Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution},
   url = {https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06652-7},
   volume = {23},
   year = {2025}
}

TY  - JOUR
ID  - 2511403
AU  - Papatheodorou, Ioanna - Blazkova, Gabriela - Bosáková, Veronika - Tomášiková, Zuzana - Spearing, Erin Rose - Klieber, Robin - Ostasov, Pavel - Štíchová, Julie - Dvončová, Martina - Mýtniková, Alexandra - Emmer, Jan - Bendíčková, Kamila - Tomáš, Tomáš - Šrámek, Vladimír - Kolovos, Petros - Holubova, Monika - Helán, Martin - Vlková, Marcela - Frič, Jan - Hortová Kohoutková, Marcela
PY  - 2025
TI  - Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution
JF  - Journal of Translational Medicine
VL  - 23
IS  - 1
SP  - 1-22
EP  - 1-22
PB  - BMC
SN  - 14795876
KW  - IL-18
KW  - Inflammation resolution
KW  - Monocyte macrophage transition
KW  - Sepsis
KW  - Recovery
KW  - Cytokine profiling
UR  - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06652-7
N2  - 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-alpha 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 NF kappa B. These changes were attenuated in the presence of TNF-alpha, thus showing a unique role of IL-18 when acting alone without its most frequent paired cytokine TNF-alpha. We further confirmed that IL-18 induces monocyte-macrophage transition and migration using human intestinal organoids. Finally, TNF-alpha/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-alpha as a novel marker of inflammation resolution, with potential implications for patient monitoring and therapeutic strategies.
ER  -

PAPATHEODOROU, Ioanna; Gabriela BLAZKOVA; Veronika BOSÁKOVÁ; Zuzana TOMÁŠIKOVÁ; Erin Rose SPEARING; Robin KLIEBER; Pavel OSTASOV; Julie ŠTÍCHOVÁ; Martina DVONČOVÁ; Alexandra MÝTNIKOVÁ; Jan EMMER; Kamila BENDÍČKOVÁ; Tomáš TOMÁŠ; Vladimír ŠRÁMEK; Petros KOLOVOS; Monika HOLUBOVA; Martin HELÁN; Marcela VLKOVÁ; Jan FRIČ a Marcela HORTOVÁ KOHOUTKOVÁ. Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution. \textit{Journal of Translational Medicine}. London: BMC, 2025, roč.~23, č.~1, s.~1-22. ISSN~1479-5876. Dostupné z: https://doi.org/10.1186/s12967-025-06652-7.

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