IL-17 is associated with disease severity and targetable inflammatory processes in heart failure

Lukas Baumhove; Bart J. van Essen; Martin M. Dokter; Sietske N. Zijlstra; Frederik E. Deiman; Jon D. Laman; Chim C. Lang; Gwenny M.P.J. Verstappen; Dirk J. van Veldhuisen; Peter van der Meer; Nils Bomer; Adriaan A. Voors

doi:10.1002/ehf2.14968

IL-17 is associated with disease severity and targetable inflammatory processes in heart failure

Lukas Baumhove, Bart J. van Essen, Martin M. Dokter, Sietske N. Zijlstra, Frederik E. Deiman, Jon D. Laman, Chim C. Lang, Gwenny M.P.J. Verstappen, Dirk J. van Veldhuisen, Peter van der Meer, Nils Bomer, Adriaan A. Voors (Lead / Corresponding author)

Cardiovascular Research

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Abstract

Aims

Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF.

Methods and results

IL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response.

Conclusions

In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.

Original language	English
Pages (from-to)	3530-3538
Number of pages	9
Journal	ESC Heart Failure
Volume	11
Issue number	6
Early online date	19 Jul 2024
DOIs	https://doi.org/10.1002/ehf2.14968
Publication status	Published - Dec 2024

Keywords

cytokines
heart failure
inflammation

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1002/ehf2.14968Licence: CC BY-NC

Final published versionFinal published version, 812 KBLicence: CC BY-NC

Cite this

Baumhove, L., van Essen, B. J., Dokter, M. M., Zijlstra, S. N., Deiman, F. E., Laman, J. D., Lang, C. C., Verstappen, G. M. P. J., van Veldhuisen, D. J., van der Meer, P., Bomer, N., & Voors, A. A. (2024). IL-17 is associated with disease severity and targetable inflammatory processes in heart failure. ESC Heart Failure, 11(6), 3530-3538. https://doi.org/10.1002/ehf2.14968

@article{02133e6d2539459f81f54f83b91c8993,

title = "IL-17 is associated with disease severity and targetable inflammatory processes in heart failure",

abstract = "Aims Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF. Methods and resultsIL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response. Conclusions In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.",

keywords = "cytokines, heart failure, inflammation",

author = "Lukas Baumhove and {van Essen}, {Bart J.} and Dokter, {Martin M.} and Zijlstra, {Sietske N.} and Deiman, {Frederik E.} and Laman, {Jon D.} and Lang, {Chim C.} and Verstappen, {Gwenny M.P.J.} and {van Veldhuisen}, {Dirk J.} and {van der Meer}, Peter and Nils Bomer and Voors, {Adriaan A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2024",

month = dec,

doi = "10.1002/ehf2.14968",

language = "English",

volume = "11",

pages = "3530--3538",

journal = "ESC Heart Failure",

issn = "2055-5822",

publisher = "Wiley",

number = "6",

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TY - JOUR

T1 - IL-17 is associated with disease severity and targetable inflammatory processes in heart failure

AU - Baumhove, Lukas

AU - van Essen, Bart J.

AU - Dokter, Martin M.

AU - Zijlstra, Sietske N.

AU - Deiman, Frederik E.

AU - Laman, Jon D.

AU - Lang, Chim C.

AU - Verstappen, Gwenny M.P.J.

AU - van Veldhuisen, Dirk J.

AU - van der Meer, Peter

AU - Bomer, Nils

AU - Voors, Adriaan A.

PY - 2024/12

Y1 - 2024/12

N2 - Aims Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF. Methods and resultsIL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response. Conclusions In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.

AB - Aims Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF. Methods and resultsIL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response. Conclusions In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.

KW - cytokines

KW - heart failure

KW - inflammation

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U2 - 10.1002/ehf2.14968

DO - 10.1002/ehf2.14968

M3 - Article

C2 - 39031992

AN - SCOPUS:85198998192

SN - 2055-5822

VL - 11

SP - 3530

EP - 3538

JO - ESC Heart Failure

JF - ESC Heart Failure

IS - 6

ER -

IL-17 is associated with disease severity and targetable inflammatory processes in heart failure

Abstract

Keywords

ASJC Scopus subject areas

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Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure

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IL-17 is associated with disease severity and targetable inflammatory processes in heart failure

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure

Cite this