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IL-6 and Diuretic Response in Acute Heart Failure
Daan C H Ceelen1, Lukas Baumhove1, Bart J van Essen1
1University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands.
Journal of Cardiac Failure
|April 27, 2026
Summary
Higher interleukin-6 (IL-6) levels in acute heart failure (AHF) patients are linked to reduced diuretic and natriuretic responses, impacting decongestion success. This suggests IL-6 may be a biomarker for poor treatment response and a therapeutic target.
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- Acute heart failure (AHF) presents significant mortality and rehospitalization risks.
- Successful decongestion is a critical therapeutic goal in AHF management.
- Elevated plasma interleukin-6 (IL-6) is observed in AHF, correlating with adverse outcomes and potentially influencing diuretic response.
Purpose of the Study:
- To investigate the relationship between plasma IL-6 levels and natriuresis and diuresis during AHF hospitalization.
- To assess the association of IL-6 with 24-hour diuretic response and clinical outcomes.
- To explore IL-6 as a potential biomarker for decongestive response in AHF.
Main Methods:
- Plasma IL-6 was measured in 273 AHF patients from the PUSH-AHF trial.
- Linear mixed-effects models assessed IL-6 associations with natriuresis and diuresis over time.
- Linear regression and mediation analyses evaluated IL-6's link to diuretic response and clinical outcomes, with external validation in the PROTECT cohort.
Main Results:
- Patients with high IL-6 exhibited lower natriuresis (adjusted p<0.001) and diuresis (adjusted p=0.011).
- IL-6 was independently associated with poorer 24-hour diuretic response (p=0.003), unlike NT-proBNP and bio-ADM.
- Impaired diuretic response mediated 44.6% of the association between elevated IL-6 and adverse clinical outcomes.
Conclusions:
- Elevated IL-6 levels are independently linked to diminished diuretic and natriuretic responses in AHF.
- IL-6 may serve as a biomarker indicating an inadequate decongestive response in AHF patients.
- IL-6 presents a potential therapeutic target for improving decongestion in AHF.
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