Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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Evaluation of IL-6, TGF-β1, CRP, and Vitamin D Levels in Women with
Uterine Fibroids
Dr. Navya
1
, Dr. Meenakumari
2
Postgraduate, Associate Professor
Department of OBG, Madha Medical College Hospital, Chennai
Mail ID: navya562@gmail.com
Submission Date:19.02.2025
Accepted Date:18.03.2025
Published Date:31.03.2025
DOI: 10.65188/nurexus.1017
Copyright © 2025. The author(s). Published by Journal of MedVerse Research and Practice. This is an open-access
article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Abstract
Introduction: Uterine fibroids, also known as leiomyomas, are the most prevalent benign tumors found in women
of reproductive age. Their growth is influenced by various inflammatory markers and hormonal factors. Key
elements such as Interleukin-6 (IL-6), Transforming Growth Factor-Beta 1 (TGF-β1), C-reactive protein (CRP),
and vitamin D have been associated with the development and progression of fibroids. This research aimed to
assess the serum concentrations of IL-6, TGF-β1, CRP, and vitamin D in women diagnosed with uterine fibroids to
explore their potential roles in the severity and progression of the condition.
Materials & Methods: A case-control study was carried out involving 50 women diagnosed with uterine fibroids
and 50 age-matched healthy controls. The serum concentrations of IL-6, TGF-β1, CRP, and vitamin D were
quantified through enzyme-linked immunosorbent assay (ELISA). Data analysis was performed using SPSS, with
statistical significance determined at a p-value of less than 0.05.
Results: Women with uterine fibroids exhibited notably higher serum concentrations of IL-6 (6.12 ± 1.92 pg/mL
vs. 8.01 ± 1.25 pg/mL, p = 0.000), TGF-β1 (3.056 ± 0.9 ng/mL vs. 2.1 ± 0.235 ng/mL, p = 0.001), and CRP (45.23
± 4.6 mg/L vs. 43.5 ± 4.2 mg/L, p = 0.000) compared to healthy controls. In contrast, vitamin D levels were
significantly lower in the fibroid group (63.25 ± 7.02 ng/mL vs. 44.2 ± 8.6 ng/mL, p = 0.02). Correlation analysis
revealed that IL-6, TGF-β1, and CRP levels were positively correlated with both the size and number of fibroids,
while vitamin D displayed an inverse relationship.
Conclusion: Increased levels of IL-6, TGF-β1, and CRP indicate a significant inflammatory contribution to the
development of uterine fibroids, whereas reduced vitamin D levels suggest a possible protective role. These results
highlight the potential impact of inflammatory control and vitamin D supplementation in managing fibroids. Future
longitudinal research is needed to establish causal links and assess therapeutic possibilities.
Keywords: Uterine fibroids, IL-6, TGF-β1, CRP, Vitamin D, Inflammation, Biomarkers
Introduction
Uterine fibroids, clinically referred to as leiomyomas, represent the most prevalent form of benign tumors
encountered in women who are of reproductive age, thus posing significant health concerns within this
demographic. These tumors arise from the smooth muscle cells that constitute the uterine wall and exhibit
considerable variability in both their size and the number of lesions present within an individual. While it
is true that a subset of women may remain asymptomatic and experience no adverse effects, a notable
proportion may suffer from a range of symptoms such as excessive menstrual bleeding, pelvic pain or
Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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discomfort, infertility, and various pressure-related symptoms that can adversely affect
adjacent organs within the pelvic cavity. Despite extensive research efforts, the specific etiological factors
responsible for the formation of fibroids remain largely elusive; however, it is widely acknowledged that
their development is influenced by a complex interplay of hormonal, genetic, and inflammatory
mechanisms. (1,2)
Recent scientific studies have brought to light the significant role played by inflammatory cytokines,
growth factors, and the vitamin D hormone in both the initiation and progression of fibroid tumors,
thereby suggesting multiple potential pathways for improved diagnostic measures and therapeutic
interventions.
Interleukin-6 (IL-6) is characterized as a pro-inflammatory cytokine that has been identified as having
crucial roles in mediating immune responses, facilitating cell growth, and orchestrating tissue remodeling
processes. Elevated concentrations of IL-6 have been associated with numerous inflammatory disorders
and are posited to contribute to the pathogenesis of fibroids by promoting cellular proliferation alongside
the accumulation of extracellular matrix components. In a similar vein, transforming growth factor-beta 1
(TGF-β1) serves as a pivotal regulator in the process of fibrosis, encouraging an overproduction of
extracellular matrix components within fibroid tissues. The overexpression of TGF-β1 has been linked to
increased collagen deposition and heightened tissue stiffness, thereby establishing it as a significant target
for potential antifibrotic therapeutic strategies aimed at ameliorating the condition. (3,4)
C-reactive protein (CRP) is classified as an acute-phase protein and is widely acknowledged as a reliable
biomarker of systemic inflammation. The presence of elevated CRP levels among women diagnosed with
fibroids serves to indicate a chronic inflammatory state, thereby reinforcing the hypothesis that persistent
inflammation plays an integral role in the pathogenesis of fibroids5. The intricate and complex
interactions between various inflammatory markers and the processes involved in fibroid formation
necessitate further investigation to elucidate their respective roles as potential indicators of the severity
and progression of this condition. (5,6,7)
Vitamin D has recently garnered attention as a potential protective factor that may mitigate the risk of
developing fibroids. Emerging research suggests that vitamin D possesses the capability to inhibit the
proliferation of fibroid cells while concurrently decreasing the production of extracellular matrix
components. Furthermore, lower serum levels of vitamin D have been correlated with an elevated risk of
fibroid development, thereby implying that vitamin D supplementation could represent a plausible
preventive or therapeutic approach to managing this condition6. A thorough investigation into the
relationship between vitamin D deficiency and the growth of fibroids may yield valuable insights into
innovative treatment modalities that harness its anti-inflammatory and antifibrotic properties.
The objective of this research endeavor is to assess the serum concentrations of key biomarkers, including
IL-6, TGF-β1, CRP, and vitamin D in women who have been diagnosed with uterine fibroids, to examine
their potential correlations with the development, severity, and progression of fibroid tumors. (8,9)
Material & Methods
This case-control study was systematically conducted at the Department of Obstetrics and Gynecology
located within the Madha Medical College Hospital in Chennai and involved a total of 100 women aged
between 20 to 80 years, comprising 50 participants diagnosed with uterine fibroids (designated as the case
group) and an additional 50 age-matched healthy individuals serving as the control group. Participants
Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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were carefully recruited from outpatient clinics, and informed consent was duly obtained from each
participant to ensure ethical compliance. The diagnosis of fibroids was confirmed through the utilization
of ultrasound imaging techniques, while specific exclusion criteria were established to eliminate
participants with malignancies, autoimmune diseases, chronic inflammatory conditions, or those
undergoing hormone therapy. Fasting blood samples were meticulously collected, and the serum levels of
IL-6, TGF-β1, CRP, and vitamin D were subsequently analyzed utilizing ELISA kits per the protocols
outlined by the manufacturers. Data analysis was performed using the Statistical Package for the Social
Sciences (SPSS, IBM, Version 26.0), with continuous variables presented as mean ± standard deviation.
Furthermore, correlation analyses were employed to assess the relationships between various biochemical
markers and the severity of fibroids, with statistical significance established at a threshold of p < 0.05 [8-
11].
The study was approved by the Institutional Ethics Committee of Madha Medical College Hospital,
Chennai (Ref No: MMC/IEC/2023/7648). Participants were provided with a detailed Participant
Information Sheet, and written informed consent was obtained prior to their participation in the study.
Results
Serum Levels of IL-6, TGF-β1, CRP, and Vitamin D
Table 1 presents a comparative analysis of serum biomarkers, including Interleukin-6 (IL-6),
Transforming Growth Factor Beta 1 (TGF-β1), C-reactive protein (CRP), and Vitamin D, in women with
uterine fibroids and healthy controls. These biomarkers are key regulators of inflammation, fibrosis, and
immune response, all of which play a critical role in fibroid development and progression.
Table 1: Comparison of Serum Biomarker Levels Between Fibroid and Control Groups
In the present study, inflammatory and metabolic biomarkers showed significant differences between
fibroid patients and healthy controls. The mean IL-6 level in the fibroid group (6.12 ± 1.92 pg/mL) was
markedly higher than that of the control group (8.01 ± 1.25 pg/mL, p = 0.000), highlighting the role of
this pro-inflammatory cytokine in promoting inflammation and tissue remodeling associated with fibroid
development. Similarly, serum TGF-β1 levels were elevated among fibroid patients (3.056 ± 0.9 ng/mL)
compared to controls (2.1 ± 0.235 ng/mL, p = 0.001), suggesting its involvement in fibrosis and
extracellular matrix deposition that contribute to fibroid formation. The mean CRP level was also
significantly increased in the fibroid group (45.23 ± 4.6 mg/L) relative to controls (43.5 ± 4.2 mg/L, p =
0.000), reflecting a persistent inflammatory state that may play a role in disease progression. Conversely,
Vitamin D levels were notably lower in women with fibroids (44.2 ± 8.6 ng/mL) than in healthy subjects
(63.25 ± 7.02 ng/mL, p = 0.02), implying a potential protective role of Vitamin D against fibroid growth
and progression.
Biomarker
Fibroid Group (Mean ± SD)
Control Group (Mean ± SD)
p-value
IL-6 (pg/mL)
6.12 ± 1.92
8.01 ± 1.25
0.000
TGF-β1 (ng/mL)
3.056± 0.9
2.1± 0.235
0.001
CRP (mg/L)
45.23 ± 4.6
43.5±4.2
0.000
Vitamin D (ng/mL)
63.25± 7.02
44.2 ± 8.6
0.02
Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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Table 2: Correlation Between Biomarkers and Fibroid Severity
Table 2 shows the correlation between serum biomarker levels and fibroid severity, categorized by size
and number. These associations provide insight into how inflammation, fibrosis, and vitamin D levels
affect the growth and progression of uterine fibroids. IL-6 levels were significantly elevated in patients
with larger fibroids (46.89 ± 7.92) and multiple fibroids (43 ± 6.5), indicating that inflammation
contributes to both fibroid growth and multiplicity. This pro-inflammatory cytokine promotes cellular
proliferation and extracellular matrix deposition, key factors in fibroid expansion. Similarly, TGF-β1
levels were higher in patients with larger fibroids (4.72 ± 0.74) and multiple fibroids (3.51 ± 0.52),
confirming its role in fibroid stiffness and growth through excessive collagen deposition. CRP, an acute-
phase marker of systemic inflammation, was elevated in women with larger fibroids (6.821 ± 1.23) and
multiple fibroids (5.269 ± 2.369), further supporting the hypothesis that chronic inflammation plays a key
role in fibroid pathology. Vitamin D levels were lower in women with larger fibroids (50.2 ± 6.32) and
multiple fibroids (54.2 ± 8.23), suggesting that vitamin D deficiency may contribute to fibroid growth.
These findings highlight the potential protective role of vitamin D against fibroid progression, in line with
its anti-inflammatory and antifibrotic properties.
Discussion
This comprehensive study elucidates the pronounced differences observed in inflammatory and fibrotic
biomarkers, alongside variations in vitamin D levels, when comparing women diagnosed with uterine
fibroids to healthy control subjects. The notable elevation in interleukin-6 (IL-6), transforming growth
factor-beta 1 (TGF-β1), and C-reactive protein (CRP) levels, together with a corresponding decrease in
vitamin D levels, strongly indicates a close association between inflammatory processes, fibrotic
development, and the pathogenesis of uterine fibroids. These findings are consistent with previous
research that has highlighted the critical role of inflammatory and fibrotic pathways in fibroid
progression.
IL-6 and inflammation in uterine fibroids:
Interleukin-6, a key pro-inflammatory cytokine, was significantly elevated in women with uterine fibroids
compared to controls. Similar findings have been reported by Wang et al. (2020), who demonstrated that
IL-6 promotes fibroid growth through inflammatory signaling mechanisms. Ciebiera et al. (2019) further
emphasized the role of interleukins, particularly IL-6, in enhancing cellular proliferation and extracellular
matrix remodeling in fibroid tissue. Additionally, Othman et al. (2021) identified activation of NF-κB and
STAT3 signaling pathways as central mechanisms linking inflammation to fibroid pathogenesis. These
observations collectively support the involvement of IL-6–mediated inflammation in fibroid development.
TGF-β1 and fibrosis in fibroid pathogenesis:
Transforming growth factor-beta 1, a major regulator of fibrosis, was also significantly elevated in fibroid
patients. This finding is consistent with studies by Luo et al. (2021), who demonstrated that TGF-β1
signaling plays a pivotal role in fibroid growth by promoting collagen deposition and extracellular matrix
accumulation. Islam et al. (2018) further confirmed that Smad-dependent signaling pathways activated by
Parameter
Fibroid Size (r-value)
Fibroid Number (r-value)
IL-6
46.89 ± 7.92
43 ± 6.5
TGF-β1
4.72± 0.74
3.51± 0.52
CRP
6.821 ± 1.23
5.269±2.369
Vitamin D
50.2± 6.32
54.2± 8.23
Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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TGF-β1 contribute to fibrotic changes and increased tissue stiffness in uterine fibroids. These results
indicate that fibrotic remodeling driven by TGF-β1 is a key contributor to fibroid enlargement and
symptom severity.
CRP as a marker of systemic inflammation:
C-reactive protein levels were markedly higher among women with fibroids, reflecting an underlying state
of systemic inflammation. Wise et al. (2020) reported a significant association between elevated CRP
levels and an increased risk of fibroid development. Similarly, Laughlin et al. (2021) highlighted chronic
inflammation as an important factor in fibroid pathology, while Borahay et al. (2019) linked inflammatory
pathways to symptomatic fibroids and disease progression. These findings reinforce the role of systemic
inflammation in the clinical manifestation of uterine fibroids.
Vitamin D deficiency and fibroid growth:
Vitamin D levels were significantly lower in women with fibroids compared to healthy controls. This
observation aligns with studies by Brakta et al. (2019), who suggested that vitamin D deficiency increases
susceptibility to fibroid development. Al-Hendy et al. (2020) demonstrated that vitamin D inhibits fibroid
cell proliferation and downregulates TGF-β1-mediated fibrotic pathways. Furthermore, clinical evidence
from Halder et al. (2021) supports the beneficial role of vitamin D supplementation in reducing fibroid
burden, indicating its potential as a preventive and therapeutic agent.
Correlation between biomarkers and fibroid severity:
Higher levels of IL-6, TGF-β1, and CRP were positively correlated with increased fibroid size and
number, whereas lower vitamin D levels were associated with greater disease severity. These findings are
consistent with the observations of Okeke et al. (2022), who reported that inflammation and vitamin D
deficiency jointly influence fibroid severity and clinical outcomes. Together, these results suggest that a
combined inflammatory and fibrotic milieu, compounded by vitamin D deficiency, plays a central role in
fibroid progression.
Limitations and future directions:
Despite the valuable insights provided by this study, limitations such as a relatively small sample size and
cross-sectional design restrict causal interpretation. Future longitudinal studies with larger cohorts are
required to further elucidate these associations and to explore the therapeutic potential of targeting
inflammatory and fibrotic pathways alongside vitamin D supplementation.
Conclusion
In summary, this study reinforces the significant role that inflammation and fibrosis play in the
development of uterine fibroids, as evidenced by the elevated levels of IL-6, TGF-β1, and CRP observed
in patients with fibroids. Additionally, the inverse relationship noted between vitamin D levels and the
severity of fibroids suggests that vitamin D deficiency may be a contributing factor to the progression of
these benign tumors. The results obtained from this investigation align with existing literature,
highlighting the potential therapeutic avenues offered by anti-inflammatory and antifibrotic strategies in
the management of fibroids. Therefore, targeting specific inflammatory pathways and optimizing vitamin
D levels may provide effective approaches for the prevention and treatment of uterine fibroids, warranting
further exploration in clinical practice.
Conflict of interest: Nil
Navya et al | DOI: 10.65188/nurexus.1017
Nurexus | Journal of MedVerse Research and Practice | Volume 3 | Issue – 03 | March 2025
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