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Cytokines and Other Biomarkers of Health Status
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Cytokines and Other Biomarkers of Health Status

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 6635

Special Issue Editors

Prof. Dr. Anna Cywińska

E-Mail Website
Guest Editor
Department of Basic and Preclinical Sciences, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, Lwowska 1, 87-100 Toruń, Poland
Interests: veterinary medicine; cytokine; horse
Prof. Dr. Ewelina Maculewicz

E-Mail Website
Guest Editor
Laboratory of Genetics, Department of Biomedical Sciences, Faculty of Physical Education, Józef Piłsudski University of Physical Education, 00-968 Warsaw, Poland
Interests: genes; nutritional; cytokine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cytokines initiate, regulate, promote and inhibit a wide variety of physiological and pathological processes in humans and animals. They act as a network which is also closely related to other molecules orchestrating to shape the biological processes involved in both health and disease. The measurements of particular biomarkers and the changes in their levels give a deeper insight into the onset of biological responses, including acute and chronic inflammation, autoimmunity, cancer, and organ failure, as well as adaptation to age-related changes and environmental conditions. Better understanding the cytokine balance not only extends our knowledge of physiology and the pathogenesis of diseases, including the early onset of pathologies, but gives an opportunity to consider the novel diagnostic and therapeutic strategies. 
This Special Issue focuses on cytokines as biomarkers of various physiological and pathological conditions as well as the interactions and balance of other biomarkers. We welcome original studies and reviews that advance and summarize the understanding of biomarkers orchestrating various biological processes as well as diagnostic trends. 

Prof. Dr. Anna Cywińska
Prof. Dr. Ewelina Maculewicz
Guest Editors

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Keywords

  • cytokine concentration
  • cytokine gene expression
  • cytokine receptors
  • biomarkers
  • pathogenesis
  • adaptation
  • homeostasis

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Published Papers (5 papers)

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Research

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19 pages, 2007 KB  
Article
Transcriptomic Insights into Tumor Necrosis Factor α’s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts
by Agnieszka Sadowska, Tomasz Molcan, Magda Słyszewska, Dariusz J. Skarzynski, Graça Ferreira-Dias and Anna Szóstek-Mioduchowska
Int. J. Mol. Sci. 2025, 26(23), 11344; https://doi.org/10.3390/ijms262311344 - 24 Nov 2025
Viewed by 415
Abstract
Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual [...] Read more.
Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of the current study was to establish the effects of TNFα on the equine endometrial fibroblast transcriptome as well as on proliferation and expression of ECM-associated factors in in vitro cultured fibroblasts derived from non-fibrotic equine endometrium. RNA-sequencing revealed changes in the expression of 737 genes (padjusted < 0.05; log2FC ≥ 1.0/log2FC ≤ −1.0) between untreated and TNFα-treated equine endometrial fibroblasts. These genes are involved in, i.a., B cell activation, proliferation and differentiation, cell cycle, canonical NF-κB signal transduction, ERK1 and ERK2 cascade, and p53 signaling pathway. Moreover, it was found that TNFα increased fibroblast proliferation and affected the expression of metalloproteinases and their tissue inhibitors in mare endometrial fibroblasts. Results of the current study highlight that TNFα modulates the expression of genes related to immune cell activation, cell fate, and ECM remodeling in in vitro cultured equine endometrial fibroblasts, suggesting TNFα contribution in development of fibrosis in the mare endometrium. Since the current study provides mechanistic insight into TNFα action, these findings provide a foundation for future research aimed at targeting TNFα-mediated pathways as potential therapeutic strategies to mitigate equine endometrial fibrosis progression. Full article
(This article belongs to the Special Issue Cytokines and Other Biomarkers of Health Status)
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10 pages, 913 KB  
Article
Does the Relationship Between Microelements (Copper, Zinc and Selenium) and Proinflammatory Proteins (IL-6, IL-8 and Tissue Factor) Have Diagnostic Value in Equine Medicine?
by Wioleta Mojsym, Sylwester Kowalik, Agnieszka Chałabis-Mazurek, Iwona Janczarek and Witold Kędzierski
Int. J. Mol. Sci. 2025, 26(21), 10429; https://doi.org/10.3390/ijms262110429 - 27 Oct 2025
Viewed by 550
Abstract
Some correlations between serum Cu, Zn and Se and cytokines have been reported in humans. Especially, the Cu:Zn ratio corresponded with inflammation. To date, relationships between microelements and proinflammatory proteins are poorly understood in horses. The aim of the study was to evaluate [...] Read more.
Some correlations between serum Cu, Zn and Se and cytokines have been reported in humans. Especially, the Cu:Zn ratio corresponded with inflammation. To date, relationships between microelements and proinflammatory proteins are poorly understood in horses. The aim of the study was to evaluate whether Cu, Zn and Se may influence turnover of IL-6, IL-8 and tissue factor (TF) in breeding and working horses. Blood samples obtained from 66 horses were analysed. There were 37 pregnant broodmares of different breeds, 13 barren broodmares and 16 race Thoroughbred horses. Serum Cu, Zn and Se concentration was determined using the gas flame atomic absorption spectrometry (GFAAS) method. Plasma IL-6, IL-8 and TF concentration was determined by the ELISA method. A coefficient correlation was carried out to compare the values of microelements studied with IL-6, IL-8 and TF using Pearson’s test. The values of IL-6 correlated significantly positively with Se and Cu:Zn ratio, IL-8 correlated positively with Cu and Cu:Zn ratio and negatively with Zn, and TF correlated positively with Cu, Cu:Zn ratio and Se. The Cu:Zn ratio varies significantly between horses, with high values occurring in horses with high levels of proinflammatory proteins, which may indicate the presence of a subclinical inflammatory process. The high variability of TF in the studied groups gives hope for the use of its determination in laboratory diagnostics of horses. Full article
(This article belongs to the Special Issue Cytokines and Other Biomarkers of Health Status)
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18 pages, 281 KB  
Article
Connections Between Gene Polymorphism and Fetlock and Hock Measurements in Polish Sport Horses
by Dorota Lewczuk, Maria Wypchło, Mateusz Hecold, Roma Buczkowska and Agnieszka Korwin-Kossakowska
Int. J. Mol. Sci. 2025, 26(19), 9645; https://doi.org/10.3390/ijms26199645 - 2 Oct 2025
Viewed by 641
Abstract
Finding the causative mutations for musculoskeletal system development and health status is of a higher priority for all sport horse breeders’ associations. Of the regulating proteins involved in animal ossification, 15 gene polymorphisms were chosen to be identified as connected with the nine [...] Read more.
Finding the causative mutations for musculoskeletal system development and health status is of a higher priority for all sport horse breeders’ associations. Of the regulating proteins involved in animal ossification, 15 gene polymorphisms were chosen to be identified as connected with the nine fetlock and 14 hock bone structures measurements of 198 horses. All measurements were taken using X-rays of the limbs, which were available at the beginning and end of the horse training. The analysis of variance (GLM, SAS program) was performed taking into account identified training and horse-connected characteristics, and gene polymorphism. The larger size of the bone structure was achieved in the fetlock for the heterozygotes of COL9A2, AOAH1, BMPER, HYAL3, and ELMO1. The heterozygotes were superior to homozygotes in the hock for the following genes: COL9A2, HYAL3, ANLN, and HYAL1. The lower homozygote values were obtained for GG in CPVL in fetlock measurements, TT for HYAL3 in fetlock, TT for ANLN in fetlock, CC for FRZB in the hock, TT for MATN in the hock, and TT for COL5A2 in the hock than their opposite homozygote and heterozygote variants. COL9A2 and HYAL3 are expressed in the same way for most of the bone structures in both joints. Full article
(This article belongs to the Special Issue Cytokines and Other Biomarkers of Health Status)

Review

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27 pages, 2094 KB  
Review
It’s a Trap!—Potential of Cathepsins in NET Formation
by Pola Pruchniak, Adrianna Niedzielska, Rafał Nejfeld, Zbigniew Wyżewski, Karolina P. Gregorczyk-Zboroch, Lidia Szulc-Dąbrowska and Małgorzata Gieryńska
Int. J. Mol. Sci. 2025, 26(22), 11213; https://doi.org/10.3390/ijms262211213 - 20 Nov 2025
Viewed by 811
Abstract
Neutrophils are first-line immune effectors in innate immunity, employing migration, phagocytosis, and neutrophil extracellular trap (NET) formation to combat infections and mediate inflammatory responses. NET formation, the regulated extrusion of chromatin and antimicrobial proteins, is crucial for pathogen clearance but can lead to [...] Read more.
Neutrophils are first-line immune effectors in innate immunity, employing migration, phagocytosis, and neutrophil extracellular trap (NET) formation to combat infections and mediate inflammatory responses. NET formation, the regulated extrusion of chromatin and antimicrobial proteins, is crucial for pathogen clearance but can lead to pathological inflammation when dysregulated. Cathepsins, a diverse family of proteolytic enzymes traditionally associated with lysosomal protein degradation, have emerged as key modulators of neutrophil functions. Serine cathepsins, including cathepsin G, and cysteine cathepsins, such as cathepsin C, regulate neutrophil migration, chemokine processing, and serine protease maturation, thereby orchestrating effective phagocytosis and antimicrobial activity. These enzymes also influence NET formation, linking classical lysosomal proteolysis to specialized immune responses. This review synthesizes current evidence on cathepsin-mediated regulation of neutrophil effector functions, highlighting their dual role in host defense and disease pathology, and discusses their potential as therapeutic targets for mitigating NET-driven inflammation in conditions such as autoimmune diseases, cancer metastasis, and ischemia–reperfusion injury. Full article
(This article belongs to the Special Issue Cytokines and Other Biomarkers of Health Status)
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15 pages, 936 KB  
Review
Anti-Cytokine Drugs in the Treatment of Canine Atopic Dermatitis
by Agnieszka Wichtowska and Małgorzata Olejnik
Int. J. Mol. Sci. 2025, 26(22), 10990; https://doi.org/10.3390/ijms262210990 - 13 Nov 2025
Viewed by 3813
Abstract
Canine atopic dermatitis (cAD) is a chronic, pruritic, inflammatory skin disease with complex immunopathogenesis involving dysregulated cytokine networks. In recent years, targeted therapies have transformed the management of cAD by directly or indirectly modulating cytokine activity. Lokivetmab, a monoclonal antibody neutralizing interleukin-31, represents [...] Read more.
Canine atopic dermatitis (cAD) is a chronic, pruritic, inflammatory skin disease with complex immunopathogenesis involving dysregulated cytokine networks. In recent years, targeted therapies have transformed the management of cAD by directly or indirectly modulating cytokine activity. Lokivetmab, a monoclonal antibody neutralizing interleukin-31, represents a breakthrough in veterinary dermatology, providing rapid and sustained reduction in pruritus with a favorable safety profile. Janus kinase inhibitors, including oclacitinib and the newer ilunocitinib, act downstream by blocking cytokine signal transduction, offering effective control of both acute and chronic phases of disease. Ciclosporin, a calcineurin inhibitor, remains a valuable immunosuppressant for long-term cAD management, while topical tacrolimus provides localized benefits. Together, these therapies mark a paradigm shift from non-specific immunosuppressants to precision medicine. In this context, precision medicine refers to therapeutic strategies that selectively target key cytokines or intracellular signaling pathways central to the pathogenesis of cAD, such as IL-31 or the JAK/STAT axis. Unlike traditional immunosuppressants such as glucocorticoids, which exert broad and non-selective immune suppression, these agents modulate defined molecular mechanisms, thereby improving efficacy and minimizing adverse effects. Consequently, they enable improved quality of life for affected dogs and their owners. Future strategies will likely focus on patient stratification and personalized approaches based on immunological endotypes. Full article
(This article belongs to the Special Issue Cytokines and Other Biomarkers of Health Status)
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