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Matteo Ferraresi¹, Giulia Pezzi¹, Silvia Beltrami¹, Giorgia Cianci¹, Gloria Maini¹, Alessia Liboni², Marcello Baroni³, Daria Bortolotti^1,*, Giovanna Schiuma^1,*, Sabrina Rizzo^1,#, Giovanni Strazzabosco^1,#

European Cytokine Network, Vol.37, No.2, pp. 41-53, 2026, DOI:10.32604/ecn.2026.083049 - 30 June 2026
Abstract Flaviviruses, including Dengue, West Nile, Zika, and Japanese encephalitis viruses, are arthropod-borne RNA viruses that pose an increasing global health threat. This review summarizes the role of nonstructural protein 1 (NS1), a multifunctional glycoprotein found in intracellular and secreted forms, as a key regulator of innate immunity. NS1 modulates several pattern recognition receptor pathways, including TLRs, RLRs, SR-B1-related mechanisms, and inflammasome platforms, thereby altering cytokine and interferon responses. Its effects are virus- and context-dependent. WNV NS1 inhibits TLR3/TRIF signaling, reducing IRF3 activation, type I interferon production, and interferon-stimulated gene expression. In contrast, DENV NS1 is More >

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Fiorella Carnevali^1,*, Maria Chiara Muollo², Lucia Biagini², Giacomo Rossi²

European Cytokine Network, Vol.37, No.2, pp. 55-77, 2026, DOI:10.32604/ecn.2026.082188 - 30 June 2026
（This article belongs to the Special Issue: Inflammation and Cytokine Biology in Chronic Diseases: Mechanisms and Therapeutic Targets)
Abstract Severe immune-mediated complications following viral infections and vaccinations, including COVID-19 and anti–SARS-CoV-2 immunization, display remarkable clinical overlap despite occurring in distinct biological contexts. In a previous hypothesis-driven work, we proposed that metabolic incorporation of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into human glycoconjugates—defined as xenosialylation—may contribute to post-infectious and post-vaccination immune dysregulation. We further suggest that this phenomenon may represent a form of “immunological chimerism”, in which host glycoconjugates incorporate non-self molecular structures that predispose the immune system to varying degrees of immune imbalance. In its most severe manifestation, this process may culminate in… More >

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Kavee Shree Sukumaran, Nelli Giribabu^*, Naguib Salleh^*

European Cytokine Network, Vol.37, No.2, pp. 79-95, 2026, DOI:10.32604/ecn.2026.078477 - 30 June 2026
Abstract Vulvovaginal candidiasis (VVC) is one of the most prevalent mucosal infections worldwide, experienced by women throughout their reproductive years. Candida albicans is involved in 85–95% of all VVC cases and given the stronger correlation between the severity of epithelial cytokine responses, rather than fungal burden, with VVC symptoms, this disease is fundamentally immunopathological. VVC is believed to be initiated by a cascade of events that leads to vaginal epithelial cell (VEC) damage. These cells act as immune sentinels and can detect fungal morphotypes as well as virulence factors through diverse pattern recognition receptors, such as TLRs,… More >

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93

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Yuyue Luo^1,#, Yikan Zheng^2,#, Jie Qin^1,#, Jinwei Liu², Yuhan Ma², Jingda Li³, Jun Li⁴, Wenlong Sun^1,*, Qian Zhang^2,*, Mengyao Li^5,6,*

European Cytokine Network, Vol.37, No.2, pp. 97-119, 2026, DOI:10.32604/ecn.2026.082885 - 30 June 2026
Abstract Cytokines, as key signaling molecules, are involved in the regulation of physiological and pathological processes such as inflammation, immunity, and cell growth. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, enable precise control of gene expression without changing the DNA sequence. Recent studies have revealed that cytokines interact with epigenetic regulation to form a dynamic and complex “cytokine-epigenetic axis”. Through metabolic reprogramming and regulation of epigenetic enzyme activity, this axis affects gene expression patterns at both transcriptional and post-transcriptional levels, thereby contributing to the initiation and progression of various diseases, including… More >

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73

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Hsing-Ju Wu^1,2, Yu-Chieh Tsai^3,*, Hung-Yu Lin^2,4,*

European Cytokine Network, Vol.37, No.2, pp. 121-135, 2026, DOI:10.32604/ecn.2026.079012 - 30 June 2026
Abstract Backgrounds: Lymph node metastasis is a critical determinant of breast cancer prognosis, yet the specific microenvironmental cytokines driving this process remain elusive. This study aims to identify key prognostic cytokines linking nodal metastasis to tumor microenvironment (TME) remodeling and to evaluate their clinical utility. Methods: A predefined panel of 176 microenvironmental genes was evaluated using differential expression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm on the TCGA-BRCA cohort to identify optimal predictors of nodal metastasis. Prognostic value was assessed via Kaplan-Meier, subgroup, and multivariate Cox regression analyses, and validated across five… More >

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An Xiong^1,2,#, Yi Tian^3,#, Xin Liang⁴, Shaoqun Liu^1,2, Chencheng Shi^1,2, Yiou Cao^1,2,*, Chang Su^1,2,*

European Cytokine Network, Vol.37, No.2, pp. 137-149, 2026, DOI:10.32604/ecn.2026.084018 - 30 June 2026
Abstract Backgrounds: Disruption of immune barrier function is considered a hallmark feature of inflammatory bowel disease. In the present study, the potential effects of the methyltransferase inhibitor procaine hydrochloride on intestinal barrier integrity, as well as T cell differentiation in the context of inflammatory bowel disease were explored. Methods: Using an experimental model of dextran sulfate sodium-induced ulcerative colitis, mice received daily treatment with either sulfasalazine (100 mg/kg) or procaine hydrochloride (45 mg/kg), or saline (10 μL/g) as a negative control, for 7 consecutive days. Subsequent analysis included disease activity index score, histopathology, expression levels of intestinal… More >

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61

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Fu Zhang^1,2, Miao Lin^1,2, Yuancong Jiang³, Fangjian Zhou^1,2,*

European Cytokine Network, Vol.36, No.1, pp. 1-5, 2025, DOI:10.1684/ecn.2025.0500
Abstract Interleukin-33 (IL-33), a key member of the IL-1 family, plays a significant role in inflammation and cancer. Its classic receptors, ST2 and IL-1 receptor accessory protein (IL-1RAcP), are predominantly expressed in immune cells such as T helper 2 (Th2) cells and mast cells. Recent studies have highlighted the involvement of IL-33 in breast cancer, demonstrating its ability to exert dual functional effects by modulating both innate and adaptive immune responses within the tumour microenvironment. However, the precise molecular mechanisms linking IL-33 to breast cancer pathogenesis and its potential as a target for molecularly targeted therapies More >

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Almagul Kurmanova^1,2, Gulfairuz Urazbayeva³, Laura Kayupova², Damilya Salimbaeva², Nurzhamal Dzhardemalieva⁴

European Cytokine Network, Vol.35, No.2, pp. 21-27, 2024, DOI:10.1684/ecn.2024.0497
Abstract The aim of the present study was to evaluate the diagnostic significance of the dynamics of cytokines and growth factors during pregnancy with and without preeclampsia. The study included 168 pregnant women at risk of hypertensive disorders. The levels of biomarkers of all pregnant women were studied at 12-16 weeks, 28-30 weeks and 36-38 weeks. These included cytokines (tumour necrosis factor-α, interferon-γ, interleukin-4) and growth factors (placental growth factor, vascular endothelial growth factor). All pregnant women were divided into two groups: 124 patients with preeclampsia and 44 without preeclampsia (control group). In patients with preeclampsia,… More >

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285

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Natália Alvarenga Borges¹, Larissa Manhães¹, Ludmilla Dias de Santana e Santana¹, Jessyca Sousa de Brito², Larissa Fonseca³, Ludmila F. M. F. Cardozo⁴, Denise Mafra^2,3,4,*,#,*

European Cytokine Network, Vol.37, No.1, pp. 1-11, 2026, DOI:10.32604/ecn.2026.0ECN78096
Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits antagonistic pleiotropy, mediating both protective and detrimental cellular effects depending on the ligand and context. AhR can be activated by a variety of endogenous and exogenous stimuli, including environmental pollutants, UVB radiation, heme, arachidonic acid metabolites, gut microbiota–derived compounds, and xenobiotics. Upon activation, AhR translocates to the nucleus, where it dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and binds to xenobiotic response elements, inducing the expression of genes involved in xenobiotic metabolism, oxidative stress responses, and inflammatory signaling. In addition to… More >

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427

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Fiorella Carnevali^1,*, Maria Chiara Muollo², Lucia Biagini², Giacomo Rossi²

European Cytokine Network, Vol.37, No.2, pp. 55-77, 2026, DOI:10.32604/ecn.2026.082188
（This article belongs to the Special Issue: Inflammation and Cytokine Biology in Chronic Diseases: Mechanisms and Therapeutic Targets)
Abstract Severe immune-mediated complications following viral infections and vaccinations, including COVID-19 and anti–SARS-CoV-2 immunization, display remarkable clinical overlap despite occurring in distinct biological contexts. In a previous hypothesis-driven work, we proposed that metabolic incorporation of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into human glycoconjugates—defined as xenosialylation—may contribute to post-infectious and post-vaccination immune dysregulation. We further suggest that this phenomenon may represent a form of “immunological chimerism”, in which host glycoconjugates incorporate non-self molecular structures that predispose the immune system to varying degrees of immune imbalance. In its most severe manifestation, this process may culminate in… More >

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Małgorzata Gryka-Marton, Anna Grabowska, Dariusz Szukiewicz

European Cytokine Network, Vol.35, No.3, pp. 38-47, 2024, DOI:10.1684/ecn.2024.0498
Abstract The blood-brain barrier (BBB) consists of a unique system of brain microvascular endothelial cells, capillary basement membranes, and terminal branches (“end-feet”) of astrocytes. The BBB’s primary function is to protect the central nervous system from potentially harmful or toxic substances in the bloodstream by selectively controlling the entry of cells and molecules, including nutrients and immune system components. During neuroinflammation, the BBB loses its integrity, resulting in increased permeability, mostly due to the activity of inflammatory cytokines. However, the pathomechanism of structural and functional changes in the BBB caused by individual cytokines is poorly understood.… More >

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Shira Cohen Rubin^1,*, Nadav Zacks¹, Ori Wand², Ophir Freund³, Evgeni Gershman³, Anna Breslavsky², Rotem Givoli-Vilensky¹, Anat Tzurel Ferber², Natalya Bilenko^1,4, Amir Bar-Shai³

European Cytokine Network, Vol.35, No.1, pp. 13-19, 2024, DOI:10.1684/ecn.2024.0494
Abstract COVID-19 vaccination and acute infection result in cellular and humoral immune responses with various degrees of protection. While most studies have addressed the difference in humoral response between vaccination and acute infection, studies on the cellular response are scarce. We aimed to evaluate differences in immune response among vaccinated patients versus those who had recovered from COVID-19. Materials and Methods: This was a prospective study in a tertiary medical centre. The vaccinated group included health care workers, who had received a second dose of the BNT162b2 vaccine 30 days ago. The recovered group included adults… More >

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Eva G. Palacios-Serrato¹, Karen Medina-Abreu¹, Gabriela Velasco-Loyden², Norma Angélica Lira-Rodríguez¹, Angeles C. Tecalco-Cruz^1,*

European Cytokine Network, Vol.36, No.4, pp. 64-73, 2025, DOI:10.1684/ecn.2025.0506
Abstract Background: Interferon-stimulated gene 15 (ISG15) is a small ubiquitin-like protein that can be conjugated to its target proteins through an enzymatic cascade known as ISGylation, thereby altering their function. Elevated levels of free ISG15 (non-conjugated) and ISGylation are observed in several cancer types, including medulloblastoma (MB) a malignant pediatric cerebellar tumor categorized into four molecular subgroups: Wingless, Sonic Hedgehog, Subgroup 3 (G3), and Subgroup 4 (G4). However, ISG15 gene expression in MB remains unexplored. In this study, we evaluated the ISG15 protein levels, the expression of the ISG15 and ISGylation system, and interferon gamma signaling… More >

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303

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Jiawen Chen^1,#, Zelin Liu^1,#, Keke Huang¹, Jinlan Li¹, Yajie Zhang¹, Dandan Chen¹, Yanjie Ruan², Ying Pan¹, Furun An¹, Yang Wan^1,*, Jiyu Wang^1,3,*, Qianshan Tao^1,*

European Cytokine Network, Vol.37, No.1, pp. 25-39, 2026, DOI:10.32604/ecn.2026.077875
Abstract Objectives: B-cell lymphoma exhibits significant clinical heterogeneity, necessitating improved biomarkers for risk stratification. C-C chemokine receptor 7 (CCR7) and trimethylation of histone H3 lysine 9 (H3K9me3) are implicated in cellular senescence and tumor invasion. While the clinical significance of their co-expression in lymphomagenesis remains unclear. This study aims to define the expression profiles of CCR7 and H3K9me3 in B-cell lymphoma, explore their correlation with aggressive clinical indicators, and evaluate their combined prognostic value. Methods: The expression of CCR7 and H3K9me3 in tumor tissues from B-cell lymphoma patients was analyzed by immunohistochemical (IHC) double-staining. The mechanistic… More >

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Karim Dorgham¹, Omaira Da Mata Jardin¹, Clara Mellot^1,2, Suzanne Mouries-Martin^1,2, Maude Calixte^1,2, Ngoc Khanh Nguyen¹, Raphael Lhote², Julien Haroche^1,2, Fleur Cohen-Aubart^1,2, Micheline Pha², Miguel Hié², Matthias Papo², François Chasset^1,2,3, Pascale Ghillani-Dalbin⁴, Hans Yssel¹, Zahir Amoura^1,2, Guy Gorochov^1,4, Alexis Mathian^1,2

European Cytokine Network, Vol.36, No.2, pp. 15-23, 2025, DOI:10.1684/ecn.2025.0502
Abstract Background: Type I interferons, which play an important role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE), are expressed at very low levels under physiological conditions. In this study, we focused on IFN-beta (IFN-β) for its potential use as a biomarker of SLE activity and compared three different technologies for its quantification in the serum of healthy donors and patients with SLE. Methods: A total of 93 serum samples from healthy donors and 463 serum samples from lupus patients were tested using either ELISA, digital ELISA based on Single Molecule Array… More >

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745

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Kamaljeet¹, Abhishek Vijukumar¹, Hardik Kumar^2,*, Shilpa Debnath², Sourabh Kosey¹

European Cytokine Network, Vol.37, No.1, pp. 13-24, 2026, DOI:10.32604/ecn.2026.078458
Abstract Cytokine storm syndromes have become a much-invoked concept to describe severe immunopathology in infectious, inflammatory, and iatrogenic diseases, but the concept is poorly defined and often mechanistically imprecise. High levels of systemic cytokines have often been viewed as indicators of immune dysfunction, and based on this notion, therapeutic interventions focused on general cytokine inhibition are proposed. Nevertheless, a growing number of clinical and experimental data dispute the notion that hypercytokinemia is necessarily pathological. The present paper reconsiders cytokine storm syndromes in the light of an evolutionary, systems-immunology model, and suggests that most cytokine amplification conditions… More >

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