JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 16, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
Khasanova
Z
.
K
., Rakhimov T.G., Eminov.R.I
Fergana Medical institute of Public Health, Fergana, Uzbekistan
INFLAMMATORY CYTOKINES AND THEIR ROLE IN WORSENING CHRONIC
HEART FAILURE
Abstract:
Background: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α),
interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) play a key role in the progression and acute
decompensation of chronic heart failure (CHF).
Objective: To investigate the relationship between circulating cytokine levels and acute
decompensation in CHF patients.
Methods: A retrospective study was conducted at the Bukhara Branch of the Republican
Scientific Center for Emergency Medical Care between 2022–2025. Fifty-six CHF patients were
divided into stable (n=28) and acute decompensated (n=28) groups. Serum cytokine levels were
assessed using ELISA, and results were analyzed using SPSS v25.
Results: Patients with acute decompensated CHF had significantly elevated levels of TNF-α
(14.2 ± 4.1 pg/mL vs. 6.5 ± 2.2; p<0.01), IL-6 (12.6 ± 3.7 vs. 5.8 ± 2.0; p<0.01), and IL-1β (9.8
± 2.6 vs. 4.2 ± 1.3; p<0.05) compared to the stable CHF group. These levels correlated with
higher NYHA class, BNP, NT-proBNP, and inflammatory markers (CRP, ESR).
Conclusion: Elevated TNF-α, IL-6, and IL-1β levels are strongly associated with acute CHF
decompensation, suggesting their utility as biomarkers and therapeutic targets. Cytokine
profiling may aid early detection and management of worsening heart failure.
Keywords:
Chronic heart failure, acute decompensation, inflammatory cytokines, TNF-α, IL-6,
IL-1β
Introduction
Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) play
significant roles in the pathogenesis and progression of chronic heart failure (CHF) by
contributing to inflammatory processes that exacerbate cardiac dysfunction. Elevated levels of
these proinflammatory cytokines have been consistently observed in CHF patients compared to
healthy controls, indicating their involvement in the disease's pathophysiology[1] [4] [6]. TNF-α,
IL-6, and IL-1β are implicated in adverse cardiac remodeling, which includes myocardial
hypertrophy, contractile dysfunction, and apoptosis of cardiac myocytes, as well as extracellular
matrix remodeling[3] [5]. These cytokines modulate the phenotype and function of myocardial
cells, suppressing contractile function in cardiomyocytes, inducing inflammatory activation in
macrophages, and promoting a matrix-degrading phenotype in fibroblasts[2]. Furthermore, TNF-
α and IL-6 levels correlate with the severity of heart failure, as evidenced by their increased
concentrations in patients with more advanced stages of the disease[10]. Despite the clear
association between these cytokines and CHF, clinical trials targeting these inflammatory
mediators have yielded disappointing results, highlighting the complexity of the cytokine
network and the challenges in developing effective anti-cytokine therapies[7] [8]. The cytokine-
induced synthesis of growth factors may also contribute to chronic fibrogenic actions,
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 16, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
particularly in heart failure with preserved ejection fraction (HFpEF)[2]. Overall, while TNF-α,
IL-6, and IL-1β are crucial in the inflammatory cascade that worsens CHF, their dual roles in
both protective and maladaptive responses complicate therapeutic targeting, necessitating further
research to delineate their specific pathways and interactions[9].
Methods:
This retrospective cohort study was conducted at the Bukhara Branch of the Republican
Scientific Center for Emergency Medical Care over a 3-year period (2022–2025). A total of 56
patients diagnosed with chronic heart failure (CHF) were included. These patients were divided
into two groups:
Group 1: Stable CHF patients (n=28)
Group 2: Patients with acute decompensated chronic heart failure (ADCHF) (n=28)
All patients underwent routine clinical and laboratory evaluations. The levels of inflammatory
cytokines—Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta
(IL-1β)—were measured using enzyme-linked immunosorbent assay (ELISA) techniques.
Statistical analysis was performed using SPSS v25.0. Data were expressed as means ± standard
deviation (SD). A
p
value < 0.05 was considered statistically significant.
Results:
Patients with ADCHF demonstrated significantly elevated levels of pro-inflammatory cytokines
compared to those with stable CHF. Among the 56 patients observed over three years (mean age
62.4 ± 9.8 years; 57% male) at the Bukhara Branch of the Republican Scientific Center for
Emergency Medical Care, those with acute decompensated chronic heart failure (ADCHF)
demonstrated significantly elevated levels of inflammatory cytokines compared to patients with
stable CHF. Mean levels of TNF-α rose to 14.2 ± 4.1 pg/mL in ADCHF versus 6.5 ± 2.2 pg/mL
in stable CHF (p < 0.01), IL-6 increased to 12.6 ± 3.7 pg/mL from 5.8 ± 2.0 pg/mL (p < 0.01),
and IL-1β rose to 9.8 ± 2.6 pg/mL from 4.2 ± 1.3 pg/mL (p < 0.05). These elevations were
strongly associated with higher NYHA class, increased BNP and NT-proBNP levels, and
elevated CRP and ESR values, supporting the presence of systemic inflammation. A positive
correlation was noted between IL-6 and NT-proBNP (r = 0.67; p < 0.01), indicating a
relationship between inflammatory activity and myocardial stress. Common comorbidities
included hypertension (75%), ischemic heart disease (64%), and diabetes mellitus (39%), all of
which may contribute to the observed inflammatory state. These findings suggest that elevated
cytokines—particularly TNF-α, IL-6, and IL-1β—not only reflect disease severity but also act as
key pathophysiological drivers in the acute decompensation of CHF. Mechanistically, TNF-α
impairs β-adrenergic signaling and promotes cardiomyocyte apoptosis, IL-6 contributes to
fibrosis and ventricular dysfunction, and IL-1β increases vascular permeability and endothelial
damage. Additionally, cytokines may interact with neurohormonal systems, further activating the
sympathetic nervous system and RAAS, thus worsening hemodynamics. These results are
consistent with previous studies that highlight cytokines as both mediators and markers in heart
failure [1–3], and they emphasize the potential of cytokine profiling as a prognostic tool and
target for novel therapeutic strategies in the management of ADCHF.
Table1. Cytokine levels and comparisons.
Cytok
Norma
Mean in
Mean
p-
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 16, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
ine
l
Range
(pg/m
L)
Stable
CHF
(n=28)
in
ADCH
F
(n=28)
val
ue
TNF-α
<8.1
6.5
14.2
<0.
01
IL-6
<7.0
5.8
12.6
<0.
01
IL-1β
<5.0
4.2
9.8
<0.
05
Discussion
Inflammation has been increasingly recognized as a central component in the pathophysiology of
chronic heart failure. Our findings support the hypothesis that acute decompensation in CHF is
associated with a surge in inflammatory cytokines. Elevated TNF-α, IL-6, and IL-1β may
directly impair myocardial function, increase endothelial permeability, and stimulate oxidative
stress, exacerbating heart failure symptoms [1]. These results align with other clinical trials
indicating cytokine overproduction during heart failure exacerbations [2]. Importantly, this
cytokine surge may serve as both a marker and a mediator of disease progression. Monitoring
cytokine profiles in CHF patients could help predict decompensation risk and guide anti-
inflammatory interventions [3]. This study’s findings are supported by growing evidence
confirming the critical role of inflammatory cytokines as both biomarkers and active participants
in the pathogenesis of acute decompensated chronic heart failure (ADCHF). Recent data show
that interleukin- 6 (IL- 6) is not only elevated during decompensation but also serves as a
powerful prognostic indicator; in a 2023 cohort, each logarithmic rise in IL- 6 was associated
with a 24% increased risk of cardiovascular death or rehospitalization in heart failure patients,
independent of BNP levels and ejection fraction status [1]. Similarly, tumor necrosis factor-alpha
(TNF- α) has been found to promote myocardial injury through mechanisms including
cardiomyocyte apoptosis, mitochondrial dysfunction, and extracellular matrix degradation—
leading to left ventricular remodeling and progressive systolic failure [2]. Interleukin-1β (IL- 1β),
another key cytokine, is known to exacerbate hemodynamic instability by increasing nitric oxide
production and vascular permeability, with elevated levels significantly associated with previous
hospitalizations, impaired NYHA status, and high NT-proBNP levels [3]. In addition to these
cytokines, novel inflammatory biomarkers such as soluble ST2 (sST2) have gained clinical
attention; sST2 levels above 35 ng/mL are strongly predictive of mortality and readmission in
ADCHF patients, providing incremental value beyond NT-proBNP and troponin [4].
Furthermore, emerging research shows that chemokines like interleukin- 8 (IL- 8) contribute to
persistent inflammation in CHF and are independently associated with worse functional
outcomes and inflammatory cell infiltration [5]. These findings together underscore that
inflammatory cytokines are not only reflective of disease severity but also active drivers of acute
decompensation, reinforcing the need for their integration into heart failure monitoring and
personalized treatment approaches.
Conclusion
This study confirms a strong association between elevated inflammatory cytokines and acute
decompensation in chronic heart failure. These markers not only reflect disease severity but may
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 16, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
also provide a target for future therapeutic strategies. Timely cytokine monitoring could be key
to preventing life-threatening heart failure exacerbations.
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