ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Heart Failure and Transplantation
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1677503
This article is part of the Research TopicHeart Failure and Inflammation: From Mechanistic Insights to Translational PerspectivesView all articles
High interleukin-8 serum levels independently predict long-term all-cause mortality in chronic heart failure
Provisionally accepted
Jan Traub*
Michael Klaus Schuhmann
Ulrich Hofmann
Gustavo Campos Ramos
Niklas Beyersdorf
Stefan Frantz
Stefan Störk
Guido Stoll
Anna Frey- University Hospital Würzburg, Würzburg, Germany
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ABSTRACT Background: Chronic heart failure (HF) is a complex syndrome with significant morbidity and mortality, where inflammation is increasingly recognized as a critical factor in its progression. This study investigated the association of cytokine and chemokine profiles with mild cognitive impairment (MCI) and long-term mortality in patients with chronic HF. Methods: Serum concentrations of 13 cytokines were measured in 145 patients from the Cognition.Matters-HF study baseline cohort using a bead-based multiplex assay. Detailed clinical and cognitive evaluations were conducted, and survival data were tracked over 10 years. Cox proportional hazards regression and logistic regression models were applied to assess independent associations with mortality and MCI. Results: No cytokine was independently associated with MCI. However, high interleukin-8 (IL-8) levels (>5.3 pg/ml) were significantly and independently associated with all-cause mortality (HR 2.30; 95% CI 1.30-4.07; p=0.004). After adjusting for age and sex, IL-8 remained a strong predictor (Adj. HR 2.28; 95% CI 1.29-4.05; p=0.005). Further adjustments for clinical and biochemical variables showed that IL-8 (Adj. HR 3.31; 95% CI 1.61-6.79; p=0.001) was the only cytokine independently associated with mortality. In the final multivariable model, IL-8 (Adj. HR 2.57; 95% CI 1.44-4.57; p=0.001) remained a significant predictor along with age, body mass index, left atrial volume index, and six-minute walk distance. Other cytokines, including IL-6 and tumor necrosis factor-α, showed no independent associations with mortality. Conclusions: These findings suggest IL-8's unique role in HF pathophysiology and its potential as a biomarker and therapeutic target. Further research is needed to validate these results and explore the clinical utility of IL-8 modulation in HF management.
Keywords: Heart Failure, Inflammation, Cytokines, Interleukin-8 (IL-8), Mortality, biomarker
Received: 31 Jul 2025; Accepted: 08 Oct 2025.
Copyright: © 2025 Traub, Schuhmann, Hofmann, Ramos, Beyersdorf, Frantz, Störk, Stoll and Frey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jan Traub, traub_j1@ukw.de
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