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Biomedicines
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The Role of Cytokines in Health and Disease: 2nd Edition
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The Role of Cytokines in Health and Disease: 2nd Edition

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

Deadline for manuscript submissions: 28 February 2025 | Viewed by 11871

Special Issue Editor

Dr. Monika Zajkowska

E-Mail Website
Guest Editor
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
Interests: neurodegenerative diseases; cancer; specific proteins; cytokines; biomarkers; non-invasive diagnosis
Special Issues, Collections and Topics in MDPI journals

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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cytokine
  • chemokine
  • neurodegenerative disease
  • cancer
  • inflammatory mediator
  • diagnosis
  • biomarker

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Related Special Issue

Published Papers (7 papers)

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Research

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11 pages, 1362 KiB  
Article
MCP-1 rs1024611 Polymorphism, MCP-1 Concentrations, and Premature Coronary Artery Disease: Results of the Genetics of Atherosclerotic Disease (GEA) Mexican Study
by Rosalinda Posadas-Sánchez, Fernando Velázquez-Sánchez, Juan Reyes-Barrera, Guillermo Cardoso-Saldaña, Frida Velázquez-Argueta, Neftali Eduardo Antonio-Villa, José Manuel Fragoso and Gilberto Vargas-Alarcón
Biomedicines 2024, 12(6), 1292; https://doi.org/10.3390/biomedicines12061292 - 11 Jun 2024
Viewed by 1121
Abstract
Monocyte chemoattractant protein-1 (MCP-1) participates in the initiation and progression of atherosclerosis. In vitro studies have reported that the MCP-1 rs1024611 polymorphism is associated with increased MCP-1 concentrations. The study aimed to define whether MCP-1 concentrations are associated with premature coronary artery disease [...] Read more.
Monocyte chemoattractant protein-1 (MCP-1) participates in the initiation and progression of atherosclerosis. In vitro studies have reported that the MCP-1 rs1024611 polymorphism is associated with increased MCP-1 concentrations. The study aimed to define whether MCP-1 concentrations are associated with premature coronary artery disease (pCAD) and to establish whether variations in the rs1024611 polymorphism increase MCP-1 concentrations. MCP-1 rs1024611 polymorphism was determined in 972 pCAD patients and 1070 control individuals by real-time PCR. MCP-1 concentrations were determined by the Bio-Plex system. In the total population, men had higher MCP-1 concentrations when compared to women (p < 0.001). When stratified by rs1024611 genotypes, higher MCP-1 concentrations were observed in AA individuals compared to GG subjects (p = 0.023). When performing the analysis considering sex, the differences remained significant in women (AA vs. GG, p = 0.028 and GA vs. GG, p = 0.008). MCP-1 concentrations were similar in pCAD patients and controls (p = 0.782). However, the independent analysis of the studied groups showed that in patients with the AA genotype, MCP-1 concentrations were significantly higher when compared to patients with the GG genotype (p = 0.009). Considering that the AA genotype increases MCP-1 concentration, we evaluated whether, in AA genotype carriers, MCP-1 concentrations were associated with pCAD. The results showed that for every ten pg/mL increase in MCP-1 concentration, the risk of presenting pCAD increases by 2.7% in AA genotype individuals. Individuals with the MCP-1 rs1024611 AA genotype present an increase in MCP-1 concentration. In those individuals, increased MCP-1 concentrations increase the risk of presented pCAD. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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18 pages, 336 KiB  
Article
The Impact of Cytokines on Coagulation Profile in COVID-19 Patients: Controlled for Socio-Demographic, Clinical, and Laboratory Parameters
by Milica Milentijević, Nataša Katanić, Bojan Joksimović, Aleksandar Pavlović, Jelena Filimonović, Milena Anđelković, Ksenija Bojović, Zlatan Elek, Siniša Ristić, Miloš Vasiljević, Jasmina Stevanović, Danica Radomirović, Nikolina Elez-Burnjaković, Nenad Lalović, Milan Kulić, Jovan Kulić and Marija Milić
Biomedicines 2024, 12(6), 1281; https://doi.org/10.3390/biomedicines12061281 - 10 Jun 2024
Viewed by 1080
Abstract
Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the [...] Read more.
Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = −0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient’s level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
15 pages, 2238 KiB  
Article
Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial
by Anouk Pijpe, Stephan G. Papendorp, Joost W. van der Heijden, Ben Vermin, Iris Ertugrul, Michael W. J. Ritt, Björn Stessel, Ina Callebaut, Albertus Beishuizen, Marcel Vlig, Joost Jimmink, Henk J. Huijgen, Paul P. M. van Zuijlen, Esther Middelkoop and Evelien de Jong
Biomedicines 2024, 12(4), 723; https://doi.org/10.3390/biomedicines12040723 - 25 Mar 2024
Viewed by 1486
Abstract
Background: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. Methods: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 [...] Read more.
Background: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. Methods: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. Results: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. Conclusions: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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19 pages, 965 KiB  
Article
The Impact of Cytokines on Health-Related Quality of Life in Adolescents with Allergic Rhinitis
by Ljiljana Krsmanović, Nenad Arsović, Dejan Bokonjić, Vladimir Nešić, Zoran Dudvarski, Dragana Pavlović, Milena Dubravac Tanasković, Siniša Ristić, Nikolina Elez-Burnjaković, Radmila Balaban, Branislava Ćurčić, Radenko Ivanović, Nikolina Vuković, Maja Vuković, Marija Milić and Bojan Joksimović
Biomedicines 2024, 12(2), 428; https://doi.org/10.3390/biomedicines12020428 - 13 Feb 2024
Cited by 2 | Viewed by 2064
Abstract
Background: Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines [...] Read more.
Background: Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines in nasal mucus may be associated with HRQoL in adolescents with AR. Methods: European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), “The Adolescent Rhinoconjunctivitis Quality of Life Questionnaire” (AdolRQLQ) and the Total 4 Symptom Score (T4SS) scoring system were administered to 113 adolescents with AR, nonallergic rhinitis (NAR) and to healthy control subjects. Nasal secretions were sampled and tested for 13 cytokines using a multiplex flow cytometric bead assay. Results: The AR group had significantly lower EQ-5D-3L (0.661 ± 0.267 vs. 0.943 ± 0.088; p < 0.001) and higher AdolRQLQ total scores (2.76 ± 1.01 vs. 1.02 ± 0.10; p < 0.001) compared to the control group. The AR group had higher concentrations of IL-1β (p = 0.002), IL-6 (p = 0.031), IL-8 (p < 0.001), IL17-A (p = 0.013) and IL-18 (p = 0.014) compared to the control group, and IL-1β, IL-6, IL17-A and IL-18 were significantly (p < 0.050) increased with disease progression. Cytokines IL-1β, IL-6, as well as severe CM, were identified as significant predictors of lower HRQoL in adolescents with AR. Conclusions: This study identified IL-1β, IL-6, as well as severe CM, as predictors of lower HRQoL in adolescents with AR. However, these results should only serve as a starting point for additional confirmation research. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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Review

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17 pages, 2622 KiB  
Review
Pigment Epithelial-Derived Factor in Pancreatic and Liver Cancers—From Inflammation to Cancer
by Sara Pączek, Monika Zajkowska and Barbara Mroczko
Biomedicines 2024, 12(10), 2260; https://doi.org/10.3390/biomedicines12102260 - 4 Oct 2024
Viewed by 780
Abstract
Gastrointestinal (GI) cancers are among the leading causes of mortality worldwide. Despite the emergence of new possibilities that offer hope regarding the successful treatment of these cancers, they still represent a significant global health burden. These cancers can arise from various cell types [...] Read more.
Gastrointestinal (GI) cancers are among the leading causes of mortality worldwide. Despite the emergence of new possibilities that offer hope regarding the successful treatment of these cancers, they still represent a significant global health burden. These cancers can arise from various cell types within the gastrointestinal tract and may exhibit different characteristics, behaviors, and treatment approaches. Both the prognosis and the outcomes of GI treatment remain problematic because these tumors are primarily diagnosed in advanced clinical stages. Current biomarkers exhibit limited sensitivity and specificity. Therefore, when developing strategies for the diagnosis and treatment of GI cancers, it is of fundamental importance to discover new biomarkers capable of addressing the challenges of early-stage diagnosis and the presence of lymph node metastases. Pigment epithelial-derived factor (PEDF) has garnered interest due to its inhibitory effects on the migration and proliferation of cancer cells. This protein has been suggested to be involved in various inflammation-related diseases, including cancer, through various mechanisms. It was also observed that reducing the level of PEDF is sufficient to trigger an inflammatory response. This suggests that PEDF is an endogenous anti-inflammatory factor. Overall, PEDF is a versatile protein with diverse biological functions that span across different tissues and organ systems. Its multifaceted activities make it an intriguing target for therapeutic interventions in various diseases, including cancer, neurodegeneration, and metabolic disorders. This review, for the first time, summarizes the role of PEDF in the pathogenesis of selected GI cancers and its potential utility in early diagnosis, prognosis, and therapeutic strategies for this malignancy. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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24 pages, 2413 KiB  
Review
Pleiotropic Action of TGF-Beta in Physiological and Pathological Liver Conditions
by Michał Jakub Braczkowski, Klaudia Maria Kufel, Julia Kulińska, Daniel Łukasz Czyż, Aleksander Dittmann, Michał Wiertelak, Marcin Sławomir Młodzik, Ryszard Braczkowski and Dariusz Soszyński
Biomedicines 2024, 12(4), 925; https://doi.org/10.3390/biomedicines12040925 - 22 Apr 2024
Cited by 2 | Viewed by 1664
Abstract
The aim of this study is to review and analyze the pleiotropic effects of TGF-β in physiological and pathological conditions of the liver, with particular emphasis on its role in immune suppression, wound healing, regulation of cell growth and differentiation, and liver cell [...] Read more.
The aim of this study is to review and analyze the pleiotropic effects of TGF-β in physiological and pathological conditions of the liver, with particular emphasis on its role in immune suppression, wound healing, regulation of cell growth and differentiation, and liver cell apoptosis. A literature review was conducted, including 52 studies, comprising review articles, in vitro and in vivo studies, and meta-analyses. Only studies published in peer-reviewed scientific journals were included in the analysis. TGF-β is a pleiotropic growth factor that is crucial for the liver, both in physiology and pathophysiology. Although its functions are complex and diverse, TGF-β plays a constant role in immune suppression, wound healing, and the regulation of cell growth and differentiation. In concentrations exceeding the norm, it can induce the apoptosis of liver cells. Increased TGF-β levels are observed in many liver diseases, such as fibrosis, inflammation, and steatosis. TGF-β has been shown to play a key role in many physiological and pathological processes of the liver, and its concentration may be a potential diagnostic and prognostic marker in liver diseases. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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22 pages, 3532 KiB  
Review
The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view
by Mihai Lazar, Mihai Sandulescu, Ecaterina Constanta Barbu, Cristina Emilia Chitu-Tisu, Darie Ioan Andreescu, Andreea Nicoleta Anton, Teodora Maria Erculescu, Alexandru Mihai Petre, George Theodor Duca, Vladimir Simion, Isabela Felicia Padiu, Cosmina Georgiana Pacurar, Ruxandra Rosca, Teodor Mihai Simian, Constantin Adrian Oprea and Daniela Adriana Ion
Biomedicines 2024, 12(3), 639; https://doi.org/10.3390/biomedicines12030639 - 13 Mar 2024
Cited by 2 | Viewed by 2515
Abstract
SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. [...] Read more.
SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: “lung fibrosis”, “fibrosis mediators”, “fibrosis predictors”, “COVID-19”, “SARS-CoV-2 infection”, and “long COVID-19”. In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)
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