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The Role of Cytokines in Health and Disease: 3rd Edition

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 20 April 2026 | Viewed by 6085

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Dr. Monika Zajkowska

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Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
Interests: neurodegenerative diseases; cancer; specific proteins; cytokines; biomarkers; non-invasive diagnosis
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Special Issue Information

Dear Colleagues,

This Special Issue predominantly covers the usefulness of the determination of cytokines in healthy patients and patients with civilization diseases, with a particular emphasis on neurodegenerative and neoplastic diseases. Despite being non-contagious, civilization diseases are often referred to as the epidemics of the 21st century because they spread globally and lead to over 80% of premature deaths. For many years, it has been observed that society is progressively ageing, which results in an increase in the number of elderly people who are most at risk of developing degenerative diseases of the central nervous system, as well as cancer. As part of this Special Issue, we are looking for new indicators allowing for early detection (even in potentially healthy patients, years before the first symptoms of the emerging disease), and thus a better prognosis of the survival of patients with selected civilization diseases. It is assumed that the introduction of the concentrations of the analyzed proteins to the diagnosis of patients with civilization diseases may facilitate the diagnosis and differentiation of these diseases, and thus enable the early initiation of treatment.

This Special Issue aims to comprehensively study the role of cytokines in health and in various diseases (mainly, but not only, the diseases of civilization, such as cancers or neurodegenerative diseases). Moreover, the aim of this Special Issue is also to understand the involvement of different cytokine groups in diagnosis and/or therapy and to investigate the new potential therapies targeting cytokines. In this Special Issue, original research articles and reviews are welcome.

Research areas may include (but are not limited to) the following:

Cytokines as prognostic factors of different diseases;
Cytokines as novel tumor markers in malignant tumors;
Cytokines in neurodegeneration;
Cytokines in neuroinflammation;
Cytokines in COVID-19;
Potential novel role of cytokines in health and disease.

I look forward to receiving your contributions.

Dr. Monika Zajkowska
Guest Editor

Manuscript Submission Information

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Keywords

cytokine
chemokine
neurodegenerative disease
cancer
inflammatory mediator
diagnosis
biomarker

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Related Special Issues

The Role of Cytokines in Health and Disease in Biomedicines (12 articles)
The Role of Cytokines in Health and Disease: 2nd Edition in Biomedicines (12 articles)

Published Papers (7 papers)

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Research

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21 pages, 1078 KB

Open AccessArticle

sTREM-1, HMGB1, CRP, PCT, sCD14-ST, IL-6, IL-10, sHLA-G, and Vitamin D in Relation to Clinical Scores and Survival in SIRS/Sepsis

by Michaela Kopcova, Anna Dobisova, Magda Suchankova, Elena Tibenska, Kinga Szaboova, Juraj Koutun and Maria Bucova

Biomedicines 2025, 13(10), 2481; https://doi.org/10.3390/biomedicines13102481 - 11 Oct 2025

Viewed by 363

Abstract

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and remains a major cause of mortality in intensive care units. Methods: We analyzed plasma levels of sTREM-1, CRP, PCT, sCD14-ST, HMGB1, IL-6, IL-10, vitamin D (VD), and sHLA-G in patients with SIRS/sepsis, and assessed their relationships with APACHE II, SOFA scores, and survival. Results: Septic patients showed significantly elevated sTREM-1, CRP, PCT, sCD14-ST, and higher neutrophil-to-lymphocyte ratio, while VD levels were markedly reduced. Logistic regression identified CRP and PCT as the strongest univariate predictors of sepsis, but after adjustment for age, sex, BMI, and comorbidities, CRP lost significance, whereas VD and sCD14-ST remained independent predictors. Prognostically, higher IL-10 levels significantly correlated with 7- and 28-day mortality and with SOFA scores, while higher VD concentrations predicted better survival. Conclusion: CRP, PCT, and sCD14-ST are reliable diagnostic biomarkers of sepsis, with sTREM-1 providing additional value for disease monitoring. After adjustment for clinical covariates, VD emerged as an independent protective factor, whereas elevated IL-10 significantly predicted 7- and 28-day mortality. These findings underscore the utility of combining inflammatory and immunoregulatory biomarkers to improve sepsis diagnostics and prognostication, warranting validation in larger multicenter cohorts. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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17 pages, 3426 KB

Open AccessArticle

Effects of Platelet-Rich Fibrin on In Vitro Periodontal Ligament Cell Functions

by Pablo Cores Ziskoven, Andressa Vilas Boas Nogueira, Jean-Claude Imber, Philipp Bani, Charlott Luise Hell, Jens Weusmann and James Deschner

Biomedicines 2025, 13(10), 2360; https://doi.org/10.3390/biomedicines13102360 - 26 Sep 2025

Viewed by 241

Abstract

Background: Periodontitis is a chronic inflammatory disease that leads to tooth loosening and ultimately tooth loss. Regenerative approaches employing bioactive substances aim to restore lost tissues. Platelet-rich fibrin (PRF) is a simple and cost-effective option, but its effects on periodontal ligament (PDL) cells under inflammatory conditions remain unclear. Objectives: This study investigated the stimulating effects of platelet-rich fibrin on molecules crucial for periodontal wound healing and tissue remodelling in periodontal ligament (PDL) cells, under normal and inflammatory conditions mimicked by TNF-α. Methods The stimulating effects of different concentrations of PRF on the gene expression of VEGF, BMP2, COX2, TNF-α, and SPP1 were analysed by real-time PCR and ELISA. In addition, the possible modulating effects of TNF-α, a pro-inflammatory cytokine associated with periodontitis, on PRF-induced effects were studied. Furthermore, cell viability, proliferation, and migration were investigated. Results: A 2–3-fold dose-dependent increase in the expression of all the aforementioned genes by PRF was observed at 24 h and 48 h. Additional incubation with TNF-α did not lead to any significant modulation of PRF-induced expression patterns, indicating that the effects of PRF were not compromised in an inflammatory environment. Functionally, PRF caused a significant 35% increase in cell migration between 24 h and 48 h, which was again not affected by a pro-inflammatory condition. Cell viability and proliferation remained largely unaffected by PRF, irrespective of the presence of TNF-α or not. Conclusions: The results suggest that PRF can promote initial periodontal wound healing even in an inflammatory environment by stimulating the expression of cytokines, growth factors and markers of osteogenic differentiation such as VEGF, BMP2 and SPP1, which are involved in angiogenesis, tissue remodelling, and/or cell migration. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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14 pages, 659 KB

Open AccessArticle

Anti-Inflammatory and Immunomodulatory Effects of 2-(3-Acetyl-5-(4-Chlorophenyl)-2-Methyl-1H-Pyrrol-1-yl)-3-Phenylpropanoic Acid

by Hristina Zlatanova-Tenisheva and Stanislava Vladimirova

Biomedicines 2025, 13(8), 2003; https://doi.org/10.3390/biomedicines13082003 - 18 Aug 2025

Viewed by 923

Abstract

Background: The pursuit of novel anti-inflammatory agents with enhanced efficacy and safety is crucial. Pyrrole-containing compounds, integral to many NSAIDs, exhibit promising anti-inflammatory properties. Compound 3f (2-(3-acetyl-5-(4-chlorophenyl)-2-methyl-1H-pyrrol-1-yl)-3-phenylpropanoic acid), a pyrrole derivative structurally inspired by the COX-2 selective inhibitor celecoxib, was evaluated for its anti-inflammatory and immunomodulatory effects. Methods: Anti-inflammatory activity was assessed in a carrageenan-induced paw edema model in Wistar rats. Compound 3f was administered intraperitoneally at 10, 20, and 40 mg/kg, either as a single dose or daily for 14 days. Diclofenac (25 mg/kg) served as the reference. Edema volume was measured by plethysmometry. Systemic inflammation was induced by lipopolysaccharide (LPS), and serum levels of the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-10 and TGF-β1 were quantified by ELISA following single and repeated administration of compound 3f. Results: Single-dose administration of compound 3f at 20 mg/kg significantly reduced paw edema at 2 h (p = 0.001). After 14 days, all tested doses significantly inhibited paw edema at all time points (p < 0.001). In the LPS-induced systemic inflammation model, repeated treatment with 40 mg/kg of compound 3f significantly decreased serum TNF-α (p = 0.032). TGF-β1 levels increased significantly after both single and repeated doses (p = 0.002 and p = 0.045, respectively), while IL-10 levels remained unaffected. Conclusions: Compound 3f exhibits potent anti-inflammatory activity, particularly after repeated dosing, reflected by reduced local edema and systemic TNF-α suppression. The marked elevation of TGF-β1 indicates a potential immunomodulatory mechanism, selectively modulating cytokine profiles without altering IL-10. These findings support compound 3f as a promising candidate for targeted anti-inflammatory therapy involving cytokine regulation. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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Review

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31 pages, 2225 KB

Open AccessReview

Interferons in Autoimmunity: From Loss of Tolerance to Chronic Inflammation

by Grigore Mihaescu, Gratiela Gradisteanu Pircalabioru, Claudiu Natanael Roznovan, Lia-Mara Ditu, Mihaela Maria Comanici and Octavian Savu

Biomedicines 2025, 13(10), 2472; https://doi.org/10.3390/biomedicines13102472 - 11 Oct 2025

Viewed by 171

Abstract

Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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21 pages, 2253 KB

Open AccessReview

Role of the Th2-like Immune Response in Obesity: IL-4 as a Metabolic Regulator and IL-13 as an Effector of Muscle Energy Metabolism

by Lucía A. Méndez-García, Helena Solleiro-Villavicencio, Nallely Bueno-Hernández, Arturo Cérbulo-Vázquez, Galileo Escobedo, Marcela Esquivel-Velázquez and Miguel A. Fonseca-Sánchez

Biomedicines 2025, 13(9), 2208; https://doi.org/10.3390/biomedicines13092208 - 9 Sep 2025

Viewed by 658

Abstract

The Th2 immune response, associated with allergic diseases and helminth infections, has emerged as a significant modulator of metabolic processes in adipose and liver tissues. Th2 cytokines, such as IL-4, IL-5, and IL-13, regulate energy metabolism, insulin resistance, and obesity-related issues. IL-4 and IL-13 play significant roles, while IL-5 mainly recruits eosinophils in visceral fat. IL-4 influences lipid metabolism via STAT6, promoting adipogenesis, lipolysis, and reducing leptin levels, thereby improving insulin resistance or inducing white adipose browning in the absence of leptin. IL-13 affects glucose metabolism by lowering gluconeogenesis and enhancing glucose control and increases energy expenditure in muscles during exercise via STAT3. Emerging therapies include recombinant cytokines, exosomes, and monoclonal antibodies targeting IL-4/IL-13 or IL-5, which are mostly approved for the treatment of allergic diseases. Their use in metabolic disorders is largely unexplored. Overall, Th2 cytokines are promising targets for obesity and metabolic diseases but require dedicated trials to assess benefits and risks. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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Other

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24 pages, 1775 KB

Open AccessSystematic Review

Role of Cytokines in Breast Cancer: A Systematic Review and Meta-Analysis

by Sebastian Ciurescu, Victor Buciu, Denis Șerban, Florina Borozan, Larisa Tomescu, Ionuț Marcel Cobec, Diana Gabriela Ilaș and Ioan Sas

Biomedicines 2025, 13(9), 2203; https://doi.org/10.3390/biomedicines13092203 - 9 Sep 2025

Viewed by 2144

Abstract

Background/Objectives: Cytokines play a fundamental role in the tumor microenvironment, influencing breast cancer progression, metastasis, and therapeutic resistance. The objective of this systematic review and meta-analysis was to evaluate the prognostic impact and therapeutic relevance of key cytokines in breast cancer, based on human studies published between 2015 and 2025. Methods: We systematically searched PubMed, Web of Science, and Scopus for eligible studies reporting on cytokine expression and clinical outcomes in breast cancer. Inclusion criteria were based on the PRISMA framework, focusing on human cohorts and excluding in vitro or animal models. Data were extracted on cytokine types, measurement methods, patient population, and outcomes. Meta-analyses were performed using random-effects models for cytokines with sufficient data, notably IL-6 and TNF-α. Results: Twenty-three studies were included. Elevated IL-6 was consistently associated with poor overall survival (pooled HR = 2.25, 95% CI 1.83–2.76), while high TNF-α levels showed a trend toward worse outcomes but without statistical significance. IL-1β, IL-8, and IL-10 were also linked to increased metastasis and reduced response to therapy. Immunosuppressive cytokines such as IL-10 and TGF-β facilitated tumor immune evasion, while IL-17 promoted inflammation and angiogenesis. Cytokines such as IL-12 and IFN-γ were associated with improved immune responses and a favorable prognosis. Conclusions: Cytokines are central mediators of breast cancer progression and immune regulation. Elevated levels of pro-inflammatory and immunosuppressive cytokines correlate with poor outcomes and may serve as prognostic biomarkers and therapeutic targets. Their integration into personalized treatment strategies holds significant clinical potential but requires further prospective validation and biomarker standardization. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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30 pages, 3316 KB

Open AccessSystematic Review

Preclinical Evidence of Curcuma longa Linn. as a Functional Food in the Management of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Rodent Studies

by Samuel Abiodun Kehinde, Zahid Naeem Qaisrani, Rinrada Pattanayaiying, Wai Phyo Lin, Bo Bo Lay, Khin Yadanar Phyo, Myat Mon San, Nurulhusna Awaeloh, Sasithon Aunsorn, Ran Kitkangplu and Sasitorn Chusri

Biomedicines 2025, 13(8), 1911; https://doi.org/10.3390/biomedicines13081911 - 5 Aug 2025

Viewed by 739

Abstract

Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active compound curcumin, has shown therapeutic promise in preclinical studies. This systematic review and meta-analysis evaluated the effects of Curcuma longa and its derivatives on MetS-related outcomes in rodent models. Methods: A comprehensive search was conducted across six databases (PubMed, Scopus, AMED, LILACS, MDPI, and Google Scholar), yielding 47 eligible in vivo studies. Data were extracted on key metabolic, inflammatory, and oxidative stress markers and analyzed using random-effects models. Results were presented as mean differences (MD) with 95% confidence intervals (CI). Results: Meta-analysis showed that curcumin significantly reduced body weight (rats: MD = −42.10; mice: MD = −2.91), blood glucose (rats: MD = −55.59; mice: MD = −28.69), triglycerides (rats: MD = −70.17; mice: MD = −24.57), total cholesterol (rats: MD = −35.77; mice: MD = −52.61), and LDL cholesterol (rats: MD = −69.34; mice: MD = −42.93). HDL cholesterol increased significantly in rats but not in mice. Inflammatory cytokines were markedly reduced, while oxidative stress improved via decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) and catalase (CAT) levels. Heterogeneity was moderate to high, primarily due to variations in curcumin dosage (ranging from 10 to 500 mg/kg) and treatment duration (2 to 16 weeks) across studies. Conclusions: This preclinical evidence supports Curcuma longa as a promising functional food component for preventing and managing MetS. Its multi-faceted effects warrant further clinical studies to validate its translational potential. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)

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