Universität zu Köln

Linz, Charlotte ORCID: 0009-0006-2777-4905, Shimabukuro-Vornhagen, Alexander ORCID: 0000-0002-2351-7294, Hesse, Nina, Probst, Lucie, Garcia Borrega, Jorge ORCID: 0000-0003-1326-1560, Eichenauer, Dennis A. ORCID: 0000-0002-1927-3514, Kochanek, Matthias ORCID: 0000-0002-4766-4651, von Bergwelt-Baildon, Michael and Böll, Boris ORCID: 0000-0002-6432-0981 (2025). Prediction of Hyperinflammatory Phenotypes in Critically Ill Patients via Routine Clinical Data and IL-6: Towards Personalized Anti-Inflammatory Therapy. International Journal of Molecular Sciences, 26 (20). MDPI. ISSN 1422-0067

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Abstract

[Artikel-Nr.: 9967] Interleukin-6 (IL-6) is a central mediator of systemic inflammation and is markedly elevated in critical illnesses, including sepsis, acute respiratory distress syndrome, and hyperinflammatory syndromes. Patient responses to immunomodulatory therapies vary, highlighting the need to better understand IL-6 regulation and its clinical implications. We retrospectively analyzed consecutive patients admitted to a medical intensive care unit in a quaternary academic center with a comprehensive cancer program, extracting clinical and laboratory data, including inflammatory markers and plasma IL-6 levels. Plasma IL-6 concentrations were measured using an electrochemiluminescence immunoassay. Survival analyses, multivariable adaptive Lasso regression, Bayesian logistic regression, and latent class analysis were performed to define determinants of IL-6 regulation, mortality, and inflammatory phenotypes. IL-6 levels were substantially elevated in sepsis (median 1150 pg/mL) and neutropenia (median 7866 pg/mL), with extreme concentrations exceeding 20,000 pg/mL when both were present. Although IL-6 across its full range was not independently predictive of intensive care unit mortality, dichotomized thresholds (≥200 pg/mL) correlated with lower survival. Advanced modeling defined a hyperinflammatory phenotype characterized by IL-6 ≥ 100 pg/mL and predicted mortality >40%, showing mortality of 58%, alongside distinct latent subgroups with heterogeneous inflammatory activity and outcomes. These results emphasize the prominent role of sepsis and neutropenia in driving IL-6 elevations and reveal inflammatory phenotypes with potential for risk stratification and targeted anti-cytokine therapy in critical illness.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Linz, Charlotte UNSPECIFIED https://orcid.org/0009-0006-2777-4905 UNSPECIFIED Shimabukuro-Vornhagen, Alexander UNSPECIFIED https://orcid.org/0000-0002-2351-7294 UNSPECIFIED Hesse, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Probst, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia Borrega, Jorge UNSPECIFIED https://orcid.org/0000-0003-1326-1560 UNSPECIFIED Eichenauer, Dennis A. UNSPECIFIED https://orcid.org/0000-0002-1927-3514 UNSPECIFIED Kochanek, Matthias UNSPECIFIED https://orcid.org/0000-0002-4766-4651 UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Böll, Boris UNSPECIFIED https://orcid.org/0000-0002-6432-0981 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-800783
Identification Number:	10.3390/ijms26209967
Journal or Publication Title:	International Journal of Molecular Sciences
Volume:	26
Number:	20
Number of Pages:	27
Date:	13 October 2025
Publisher:	MDPI
ISSN:	1422-0067
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO)
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language interleukin-6 ; cancer ; neutropenia ; inflammation ; sepsis ; cytokine storm English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80078