ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

CORRELATION BETWEEN FERRITIN, IL-6 AND IL-1Β:

INFLAMMATORY AND THERAPEUTIC IMPLICATIONS IN

CARDIOVASCULAR DISEASES

Marcelo Flavio Gomes Jardim Filho1

Abstract: Inammation plays a central role in the pathogenesis of cardiovascular diseases (CVDs),

with the pro-inammatory cytokines IL-6 and IL-1β exerting direct inuence on atherosclerosis

progression, endothelial dysfunction, and adverse cardiovascular outcomes. This article reviews the

correlations between ferritin, an inammatory and metabolic biomarker, and the cytokines IL-6

and IL-1β, emphasizing their relevance in chronic inammatory states and their association with

cardiovascular dysfunction. Ferritin, often elevated in response to IL-6 and IL-1β activity, reects

both an attempt by the organism to mitigate oxidative damage and a marker of inammatory

aggravation. Recent studies, including clinical trials with anti-inammatory agents such as

canakinumab, colchicine, and tocilizumab, suggest that targeted inhibition of these inammatory

pathways can signicantly improve cardiovascular outcomes. Finally, this review highlights the need

for personalized therapeutic strategies, considering patients’ inammatory proles and biomarkers,

to optimize clinical interventions and improve prognosis in CVDs.

Keywords: Ferritin; IL-6; IL-1β; inammation; cardiovascular diseases; biomarkers; atherosclerosis.

1 Cardiologist, Specialist in Cardiology from SBC, Specialist Certicate in Hypertension from

the Brazilian Society of Hypertension, Major Doctor of the Military Police of RJ, On-Call Doctor at

the Coronary Unit of the Salgado Municipal Hospital, Municipal Public Servant

Introduction

Ferritin, an essential protein for iron metabolism, performs the function of intracellular sto-

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

rage of this mineral, being able to protect it in its protein structure. After the reduction of ferric iron

(Fe³+) to ferrous iron (Fe²+) by the action of duodenal cytochrome B, iron can be absorbed by entero-

cytes, enabling their transit and cellular storage (Kowdley et al., 2020).

Figure 1: Cellular metabolism of iron - (A) Iron from the diet is absorbed by enterocytes. ( B ) Ma-

crophages participate in the process of recycling iron from erythrocytes. (C) Hepatocytes act as the

main cellular site for iron storage. Abbreviations: CD163—Cluster of differentiation 163, hemoglo-

bin-haptoglobin receptor; CD91—Cluster of differentiation 91, also known as Protein 1 related to the

low-density lipoprotein receptor (LRP1) or α2-macroglobulin receptor; CP—Ceruloplasmin; Dcy-

tb—Duodenal cytochrome B; DMT1—Divalent metal carrier 1; FPN—Ferroportina; FT—Ferritin;

Hb—hemoglobin; HCP1—Heme transporter protein 1; HEPH—Hephaestus; HMOX—Heme oxyge-

nase; HP—Haptoglobin; HPX—Hemopexin; PCBP1—Poly(RC)-binding protein 1; Tf—transferrin;

TfR—Transferrin receptor

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

Source: Fonseca, 2023

Ferritin comes in two distinct forms: when it is devoid of iron, it is called apoferritin, with

a molecular weight of around 440 kilodaltons; in the presence of iron, its structure changes, forming

holoferritin, which can reach up to 900 kilodaltons (Carrillo et al., 2015).

From a structural point of view, ferritin is composed of 24 monomers distributed in light (L)

and heavy (H) subunits, whose distribution is dependent on the tissue in question. The L subunit pre-

dominates in organs such as the liver, spleen, and bone marrow, while the H subunit manifests itself

more intensely in the heart (Mahroun et al., 2022).

Its main biological function is to store iron in a non-toxic way, preventing its participation

in Fenton reactions, in which interactions with hydrogen peroxide could generate hydroxyl free ra-

dicals. This mechanism is exploited by neutrophils and macrophages as part of the innate immune

response, in an attempt to eliminate phagocytosed microorganisms (Slaats et al., 2016). At the same

time, ferritin is essential for the balance of physiological iron levels, being a sensitive marker both for

the identication of iron deciency and for the evaluation of overload states, in which iron tends to be

deposited in macrophages in the form of hemosiderin (Ruscitti et al., 2022).

Iron metabolism is also largely inuenced by inammatory and infectious processes, in

which bacterial particles, such as lipopolysaccharide, and pro-inammatory cytokines, such as in-

terleukins 1β, 6, 18 and Tumor Necrosis Factor (TNF), promote the downregulation of ferroportin 1,

mediated by hepcidin. This hormonal interaction reduces the release of iron into the plasma, favoring

its accumulation in hepatocytes and macrophages and increasing the translation of ferritin by the

iron-response protein (Kowdley et al., 2020; Carrillo et al., 2015; Slaats et al., 2016).

Other physiological and hormonal conditions, such as variations in the levels of thyroid hor-

mones, cortisol, prostaglandins, changes in intracellular messengers, and states of hypoxia, ischemia,

or hyperoxia, also modulate serum ferritin levels, reinforcing the complexity of its regulation in dif-

ferent metabolic and pathological states.

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

The ferritin H subunit has an immunomodulatory role, being responsible for reducing iron

uptake by transferrin, an essential element for cell proliferation and differentiation. This action is re-

ected in the inhibition of processes such as blastogenesis, myelopoiesis, and T lymphocyte activation

(Carrillo et al., 2015; Slaats et al., 2016).

Ferritin, in addition to its classic role in iron metabolism, is also involved in innate and adap-

tive immunity, acting as an acute-positive phase protein. Its hepatic expression increases in response

to stimuli such as tissue injury, trauma, infections, autoimmune diseases, and neoplasms (Mahroun et

al., 2022; González et al., 2010; Urquizo et al., 2019).

During the acute inammatory response, plasma ferritin levels peak within the rst 24 to

48 hours, predominantly in the form of H-subunit monomers. This increase aims to restrict the avai-

lability of iron for free radical reactions, negatively modulate antibody synthesis by B lymphocytes,

and suppress myelopoiesis and T lymphocyte activation (Urquizo et al., 2019; Carrillo et al., 2015).

In the molecular context, ferritin H exerts negative feedback regulation on the chemokine

receptor CXCR4, an important cofactor in the activation of mitogenesis-activating protein kinase

(MAPK). This effect, in turn, reduces the proliferation, differentiation, and migration of inamma-

tory cells, while also promoting the synthesis and release of IL-10, a cytokine with anti-inammatory

properties (Li et al., 2006; Gray et al., 2001).

In parallel, ferritin can also activate inammatory pathways through interaction with TIM-2

(T-cell/Transmembrane Immunoglobulin and Mucin Domain) proteins, triggering the release of in-

ammatory mediators such as IL-6, inducible nitric oxide synthetase, and other mediators regulated

by the NF-κB pathway, often activated by protein kinase (Carrillo et al., 2015).

The increase in IL-6 levels in situations of systemic inammation is widely recognized as

one of the main stimuli for hepatic ferritin production, being accompanied by the regulation of hep-

cidin, a key hormone in the control of iron bioavailability. This increase, which occurs in response

to inammatory stimuli, reects a physiological adaptation to limit the extracellular availability of

iron, avoiding its participation in oxidative processes (Volp, 2008), where the simultaneous presence

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

of elevated levels of IL-1β intensies this phenomenon, given its role in the amplication of local in-

ammatory responses, particularly in the vascular endothelium, where it contributes to the activation

of endothelial cells and the expression of mediators pro-inammatory drugs (Urquizo et al., 2019).

When considered in the context of cardiovascular diseases, the correlation between ferritin,

IL-6 and IL-1β raises important questions about the mechanisms that relate systemic inammation

to endothelial dysfunction and the development of structural changes in the vascular wall. Elevated

ferritin levels, often observed in chronic inammatory states, can be interpreted as a reection of an

immunometabolic response that aims to mitigate the damage caused by oxidative stress, while par-

ticipating in positive feedback loops that intensify the activation of inammatory mediators, such as

IL-6 itself (Katkenov, et al, 2024).

Furthermore, the interaction between these cytokines and ferritin suggests a pathway throu-

gh which iron metabolism, often altered under inammatory conditions, can indirectly inuence

processes crucial for cardiovascular homeostasis. For example, changes in iron bioavailability may

interfere with lipid metabolism and endothelial functionality, while the proinammatory state asso-

ciated with IL-6 and IL-1β may predispose to the formation of vascular lesions (Justi, et al., 2019).

Thus, the correlation between ferritin, IL-6 and IL-1β highlights the intersection of in-

ammatory and metabolic processes in the cardiovascular context, pointing to the need for further

investigations that explore the role of these mediators in the progression of cardiovascular conditions,

with a view to understanding the underlying mechanisms of this interaction at both a systemic and

local level.

Materials and Methods

A systematic literature review was conducted using the PubMed and Embase databases, with

the aim of identifying relevant studies published between January 2014 and December 2024. The se-

arch strategy was structured based on keywords and terms indexed in the Medical Subject Headings

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

(MeSH) related to cardiovascular diseases and inammatory mediators, including “Cardiovascular

diseases”, “Interleukin-6”, “Interleukin-1β”, “Inammation” and “Biomarkers”. The search was limi-

ted to articles published in English and submitted to peer review, with the intention of encompassing

all studies investigating the roles of IL-6 and IL-1β in the context of cardiovascular diseases.

The inclusion criteria established that studies should specically address the role of IL-6

and/or IL-1β in cardiovascular diseases, have been published within the delimited period, include

relevant human and animal models of cardiovascular pathology, and present results related to clinical

outcomes, molecular mechanisms, or therapeutic interventions targeting the cytokines in question.

Studies that did not directly focus on cardiovascular diseases were excluded, as well as case reports

and editorials that did not contain original data or presented insufcient data for inclusion in the

analysis.

The collected data were qualitatively synthesized, with the purpose of presenting a com-

prehensive analysis of the roles played by IL-6 and IL-1β in the context of cardiovascular diseases.

When feasible, a meta-analysis was performed to estimate the effect sizes of cytokines on the clinical

outcomes evaluated.

Findings

Djahanpour et al. (2023) conducted a systematic review covering 17 studies and identied a

strong association between elevated IL-6 and IL-8 levels and the presence of peripheral arterial dise-

ase (PAD). Signorelli et al. (2016) described signicant elevations in serum IL-6 levels (11.8 ± 1.2 ng/

dL) in patients with PAD, evidencing a systemic inammatory state in these individuals. In patients

with chronic limb ischemia at risk of amputation (CLTI), Gremmels et al. (2019) associated elevated

IL-6 concentrations with an increased risk of amputations, reinforcing the role of this cytokine as a

mediator in severe ischemia conditions. DePalma et al. (2021) observed that ferritin levels correlated

with IL-6 levels in patients with PAD, suggesting a relationship between iron metabolism and vascu-

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

lar inammation.

The inammatory response associated with clinical management was also investigated.

Sokolik et al. (2021) reported a signicant decrease in IL-6 levels, observed both 24 hours and six

months after angioplasty and stenting, indicating a reduction in the inammatory process resulting

from the therapeutic intervention (Sokolik, et al., 2021). Guo et al. (2020) suggested that elevated con-

centrations of IL-6 have greater predictive power for in-stent restenosis compared to high-sensitivity

C-reactive protein (hs-CRP), underscoring its potential utility as a diagnostic marker in post-inter-

vention complications (Guo, et al., 2020). In post-myocardial infarction patients, Tardif et al. (2019)

identied that colchicine treatment was effective in reducing IL-6 levels, indicating therapeutic anti-

-inammatory effects of the medication (Tardif, et al, 2019).

Martínez et al. (2015) corroborated these ndings by demonstrating that colchicine signi-

cantly decreased serum concentrations of IL-6, IL-1β, and IL-18 in patients with acute coronary syn-

drome (ACS), reinforcing the positive impact of this intervention on inammation control (Gotsman,

et al, 2014).

IL-1β, a pro-inammatory cytokine known to be involved in the progression of atherosclero-

sis and in the pathogenesis of myocardial infarction, has also been investigated as a therapeutic target.

Martínez et al. (2015) demonstrated that colchicine substantially reduces IL-1β levels in patients with

ACS, evidencing its role in controlling the inammatory state associated with cardiovascular disease

(Martinez, et al., 2015).

Similarly, Gotsman et al. (2014) described an association between elevated IL-1β levels and

worse outcomes in patients with heart failure, highlighting the impact of this cytokine on the evolu-

tion of heart disease. Ridker et al. (2017), in turn, provided robust evidence showing that the use of ca-

nakinumab, an IL-1β inhibitor, reduced concentrations of this cytokine and was associated with lower

rates of cardiovascular events. These results point to the relevance of IL-1β blockade as a strategy

for reducing inammation and improving clinical outcomes in patients with cardiovascular diseases

(Ridker et al. 2017).

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

The studies analyzed emphasize the central role of IL-6 and IL-1β as inammatory mediators

in cardiovascular diseases. In different conditions, such as PAD, ACS, heart failure, and post-inter-

vention complications, these cytokines not only reect the inammatory state, but are also indicative

of prognosis and potential therapeutic targets. The detailed analysis of the methodologies employed,

including the methods of cytokine measurement and the clinical outcomes evaluated, allows us to

consolidate the understanding of the molecular mechanisms underlying these conditions, in addition

to guiding the development of new therapeutic approaches.

Discussions

The review presented here emphasizes the central role of IL-6 and IL-1β in the pathogenesis

and progression of cardiovascular diseases (CVDs), with elevated levels of these cytokines consis-

tently associated with adverse clinical outcomes, such as increased risk of myocardial infarction,

heart failure, and increased mortality. These ndings not only reinforce the relevance of inammation

as an underlying mechanism for CVDs, but also suggest that therapeutic strategies targeting these

cytokines may contribute to the modulation of inammation and, potentially, to the reduction of car-

diovascular complications.

In the context of CVDs, inammation plays a critical role, integrating immunological and

metabolic factors that culminate in endothelial dysfunction and the progression of atherosclerosis.

IL-6, a multifunctional cytokine, regulates the immune response, the inammatory process, and he-

matopoiesis. This molecule is produced by a wide variety of cells, including macrophages, broblasts,

and endothelial cells, in response to infections, tissue injury, and chronic inammatory stimuli.

IL-6 promotes the synthesis of acute-phase proteins, such as C-reactive protein (CRP), a

marker widely used to monitor systemic inammation. However, elevated levels of IL-6 are not mere

reections of the inammatory state, but also play an active role in the progression of CVDs, contri-

buting to endothelial dysfunction, atherosclerotic plaque instability, and the development of cardio-

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

vascular events, such as infarction and heart failure.

IL-1β, in turn, plays a key role in amplifying the inammatory response. This cytokine is

produced primarily by activated macrophages and exerts its effects by promoting the activation of

endothelial cells and the recruitment of leukocytes to the site of inammation. These actions directly

contribute to the advancement of the atherosclerotic process, from the initial phases of monocyte re-

cruitment and foamy cell formation to the advanced stages, with the development of unstable lesions.

In the vascular environment, IL-1β is also able to increase the expression of adhesion mo-

lecules, such as ICAM-1 and VCAM-1, facilitating the inltration of monocytes that differentiate

into macrophages and phagocytize oxidized lipoproteins (oxLDL), characteristic of atherosclerotic

plaques. This inammatory cycle perpetuates the progression of atherosclerosis and, by extension,

increases the likelihood of serious cardiovascular events.

In addition, IL-6 and IL-1β exert synergistic effects at various stages of atherosclerosis deve-

lopment. IL-6, when binding to its receptor (IL-6R), activates intracellular signaling pathways, such

as JAK/STAT, which promote the expression of genes related to inammation, cell proliferation, and

apoptosis. This chronic signaling maintains a pro-inammatory vascular environment, contributing

to plaque instability and increased risk of cardiovascular events. On the other hand, IL-1β, activated

by the NLRP3 inammasome in response to stimuli such as cholesterol crystals, intensies vascular

inammation by increasing the production of pro-inammatory cytokines, which amplify immune

cell recruitment and vascular remodeling.

Ferritin is often elevated in response to systemic inammation mediated by IL-6 and IL-1β.

Its increase reects the body’s attempt to sequester intracellular iron, reducing the availability of free

iron for oxidative reactions that could intensify oxidative stress and endothelial damage. Studies in-

dicate that elevated ferritin levels are associated not only with exacerbated inammatory processes,

but also with the development of atherosclerosis, underscoring its role as an inammatory marker in

CVDs (Gerônimo, et al., 2023).

Recent clinical trials have demonstrated the potential of anti-inammatory therapies in the

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

management of cardiovascular disease, reinforcing the importance of inammation as a therapeutic

target. The CANTOS trial, which evaluated the use of canakinumab, an IL-1β inhibitor, highlighted

the signicant reduction in recurrent cardiovascular events in patients with a history of myocardial

infarction. These results corroborate the role of IL-1β in the pathogenesis of atherosclerosis and in the

development of cardiovascular complications, pointing to the efcacy of interventions targeting this

cytokine in severe inammatory contexts.

Another relevant study, the Colchicine Cardiovascular Outcomes Trial (COLCOT), evalua-

ted low-dose colchicine, an anti-inammatory agent widely used in the treatment of diseases such

as gout, demonstrating that the drug signicantly reduced the risk of recurrent ischemic events in

patients who had recently suffered acute myocardial infarction. These ndings suggest that colchi-

cine may be repositioned as a therapeutic option to reduce inammation and improve prognosis in

cardiovascular conditions.

Tocilizumab, an IL-6 receptor antagonist, was evaluated in the ASSAIL-MI study, which

investigated its effects in patients with ST-segment elevation myocardial infarction (STEMI). This

trial demonstrated that early administration of the drug was able to improve myocardial salvage and

reduce markers of systemic inammation, such as high-sensitivity C-reactive protein (hs-CRP) le-

vels. These results underscore the potential of therapies that modulate IL-6-related pathways in the

management of STEMI patients, particularly in early stages.

The aforementioned studies reinforce the relevance of anti-inammatory therapies in the

treatment of cardiovascular diseases and suggest that personalized approaches, adjusted to the indivi-

dual inammatory prole of each patient, can increase the effectiveness of these interventions. In the

context of acute myocardial infarction (AMI), for example, the control of myocardial inammation

has become both a prognostic and therapeutic priority. The initial inammation after AMI, although

necessary for necrotic tissue removal and tissue repair, can become deleterious if exacerbated, leading

to worse ventricular remodeling and a higher risk of heart failure.

In this sense, Matter et al. (2023) highlighted the importance of anti-inammatory strategies

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

targeting the IL-1 and IL-6 pathways, emphasizing that early interventions appropriate to the patient’s

inammatory prole can mitigate the adverse effects of uncontrolled inammation. IL-1 and IL-6

inhibitors have shown promise in reducing excessive inammation, contributing to the control of

post-AMI cardiac remodeling. In addition, approaches that take into account the ideal time for inter-

vention and the inammatory burden of each patient seem to be determinant for the efcacy of the

treatment.

Additionally, the correlation between elevated levels of IL-1β and IL-6 and biomarkers of in-

ammation, such as ferritin, reinforces the importance of integrating the analysis of these inamma-

tory mediators into clinical management. Ferritin, as an acute-phase protein, is often elevated in

response to the activity of cytokines such as IL-6, reecting the body’s attempt to sequester free iron

and reduce oxidative stress. High ferritin levels, together with high concentrations of IL-6 and IL-1β,

have been observed in inammatory cardiovascular conditions, suggesting that these mediators act on

an interconnected axis, promoting the perpetuation of the inammatory state.

Final Thoughts

The present review highlighted the intersection between inammatory processes, immune

mediators, and the regulation of iron metabolism in the context of cardiovascular diseases. It was

evidenced that IL-6 and IL-1β play central roles in the pathogenesis of these conditions, not only as

inammatory mediators, but also as potential therapeutic targets. These mediators are closely linked

to ferritin, whose elevation reects the body’s attempt to mitigate inammatory and oxidative dama-

ge, but also points to its contribution to the progression of pathological states.

The studies analyzed reinforce that ferritin, mediated by the inammatory activity of cy-

tokines such as IL-6, is not only a marker, but also an active participant in the worsening of endo-

thelial dysfunctions, oxidative stress, and vascular remodeling. Elevated ferritin and cytokine levels

consistently correlate with adverse cardiovascular outcomes, including increased risk of ischemic

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

events, progression of atherosclerosis, and mortality.

Recent clinical trials, such as those investigating canakinumab, colchicine, and tocilizumab,

offer robust evidence of the potential of anti-inammatory interventions in the management of car-

diovascular disease. These results reinforce the need to integrate personalized therapeutic strategies

that consider the individual inammatory prole and biomarkers, such as ferritin, to optimize clinical

outcomes.

In view of this, further investigations that correlate ferritin, IL-6, and IL-1β are essential to

broaden the understanding of the mechanisms underlying cardiovascular inammation and to vali-

date specic therapeutic interventions. The integration of this knowledge into clinical practice can

contribute to a more effective and targeted approach to the treatment of patients with cardiovascular

diseases, promoting both prevention and improvement of long-term outcomes

REFERENCE

CARRILLO, E.; et al. Ferritin’s structural and regulatory role in cellular processes. Journal of Cellu-

lar Physiology, 2015. Available at: https://onlinelibrary.wiley.com. Accessed on: 20 nov. 2024.

DEPALMA, Ralph G.; HAYES, Virginia W.; O’LEARY, Timothy J. Optimal serum ferritin level

range: Iron status measure and inammatory biomarker. Metallomics, v. 13, n. 6, p. mfab030, 2021.

DJAHANPOUR, Niousha et al. A systematic review of interleukins as diagnostic and prognostic

biomarkers for peripheral artery disease. Biomolecules, v. 13, n. 11, p. 1640, 2023.

FONSECA, Óscar et al. New Perspectives on Circulating Ferritin: Its Role in Health and Disease.

Molecules, v. 28, n. 23, p. 7707, 2023.

GERÔNIMO, Glaucio Mauren da Silva et al. Cardiovascular risk and its association with inamma-

tory biomarkers in dialysis chronic kidney disease. 2023.

GOLDSBOROUGH, Earl; OSUJI, Ngozi; BLAHA, Michael J. Assessment of cardiovascular disease

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

risk: a 2022 update. Endocrinology and Metabolism Clinics, v. 51, n. 3, p. 483-509, 2022.

GONZÁLEZ, P. H.; et al. Biomarkers of inammation and their cardiovascular implications. Archi-

ves of Cardiovascular Diseases, 2010. Available at: https://www.archives-cardiovascular.com. Acces-

sed on: 20 nov. 2024.

GOTSMAN, Israel et al. Impaired fasting glucose: a predictor of reduced survival in patients with

heart failure. European Journal of Heart Failure, v. 16, n. 11, p. 1190-1198, 2014.

GRAY, E.; et al. Iron metabolism and the vascular response in cardiovascular disease. Cardiovascular

Research, 2001. Available at: https://academic.oup.com. Accessed on: 17 nov. 2024.

GREMMELS, Hendrik et al. A pro-inammatory biomarker-prole predicts amputation-free survi-

val in patients with severe limb ischemia. Scientic reports, v. 9, n. 1, p. 10740, 2019.

GUO, Songlin et al. Six-month results of stenting of the femoropopliteal artery and predictive value of

interleukin-6: Comparison with high-sensitivity C-reactive protein. Vascular, v. 28, n. 6, p. 715-721,

2020.

JUSTI, Amanda; TATSCH, Pamela; SIQUEIRA, Luciano Oliveira. Ferritin: biomarker of cardiovas-

cular diseases in diabetic patients. ABCS Health Sciences, v. 44, n. 1, 2019.

KATKENOV, Nurlubek et al. Systematic Review on the Role of IL-6 and IL-1β in Cardiovascular

Diseases. Journal of Cardiovascular Development and Disease, v. 11, n. 7, p. 206, 2024.

KOWDLEY, K. V.; et al. Ferritin and hepcidin in iron regulation: Implications for health and disease.

Nature Reviews Gastroenterology & Hepatology, 2020. Available at: https://www.nature.com. Acces-

sed on: 17 nov. 2024.

LI, W.; et al. Cytokines and ferritin: The immune-inammatory axis in disease. Immunology Re-

views, 2006. Available at: https://www.immunology.com. Accessed on: 20 nov. 2024.

LIBRA, M. et al. Analysis of G (-174) C IL-6 polymorphism and plasma concentrations of inamma-

tory markers in patients with type 2 diabetes and peripheral arterial disease. Journal of clinical patho-

logy, v. 59, n. 2, p. 211-215, 2006.

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

MAHROUN, M.; et al. Ferritin: Beyond iron storage, its role in immunity and inammation. Clinical

Immunology, 2022. Available at: https://www.sciencedirect.com. Accessed on: 17 nov. 2024.

MARTÍNEZ, Gonzalo J. et al. Colchicine acutely suppresses local cardiac production of inamma-

tory cytokines in patients with an acute coronary syndrome. Journal of the American Heart Associa-

tion, v. 4, n. 8, p. e002128, 2015.

PARRY-JONES, Adrian R. et al. Phase II randomised, placebo-controlled, clinical trial of interleukin-1

receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH).

European Stroke Journal, v. 8, n. 3, p. 819-827, 2023.

RAMALLAL, Raul et al. Dietary inammatory index and incidence of cardiovascular disease in the

SUN cohort. PloS one, v. 10, n. 9, p. e0135221, 2015.

RIDKER, Paul M. et al. C-reactive protein and parental history improve global cardiovascular risk

prediction: the Reynolds Risk Score for men. Circulation, v. 118, n. 22, p. 2243-2251, 2008.

SIGNORELLI, Salvatore Santo et al. Plasma levels of inammatory biomarkers in peripheral arterial

disease: results of a cohort study. Angiology, v. 67, n. 9, p. 870-874, 2016.

SLAATS, J.; et al. Inammatory pathways and ferritin: The bridge between iron metabolism and

immunity. Current Opinion in Hematology, 2016. Available at: https://journals.lww.com. Accessed

on: 20 nov. 2024.

SOYSAL, Pinar et al. Inammation, frailty and cardiovascular disease. Frailty and cardiovascular

diseases: Research into an elderly population, p. 55-64, 2020.

TAKAMURA, Taka-aki et al. Circulating malondialdehyde-modied low-density lipoprotein (MDA-

-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral

artery disease (PAD). Atherosclerosis, v. 263, p. 192-197, 2017.

TARDIF, Jean-Claude et al. Efcacy and safety of low-dose colchicine after myocardial infarction.

New England journal of medicine, v. 381, n. 26, p. 2497-2505, 2019.

ISSN: 2763-5724 / Vol. 04 - n 06 - ano 2024

URQUIZO, R.; et al. Elevated ferritin in inammatory and infectious conditions: A critical analysis.

Journal of Inammation Research, 2019. Available at: https://www.dovepress.com. Accessed on: 20

nov. 2024.

VOLP, Ana Carolina Pinheiro et al. Inammation biomarkers capacity in predicting the metabolic

syndrome. Brazilian Archives of Endocrinology & Metabology, v. 52, p. 537-549, 2008.