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Simone Negrini^1,2,*, Stefania Nicola^1,2, Iuliana Badiu^1,2, Anna Quinternetto^1,2, Ilaria Vitali^1,2, Luca Lo Sardo^1,2, Luisa Brussino^1,2
European Cytokine Network, Vol.37, No.3, pp. 151-168, 2026, DOI:10.32604/ecn.2026.083788 - 28 September 2026
Abstract Interleukin-18 (IL-18) is a pleiotropic IL-1-family cytokine whose clinical relevance depends strongly on context. A central reason is that IL-18 activity is constrained by interleukin-18 binding protein (IL-18BP), a high-affinity endogenous antagonist that limits the free, bioactive cytokine fraction. This review re-examines the IL-18/IL-18BP axis across a clinical gradient from barrier dysfunction and allergic disease, through systemic autoimmunity, to Still disease, macrophage activation syndrome, hemophagocytic lymphohistiocytosis, and monogenic IL-18opathies. We emphasize that total IL-18 elevation does not necessarily imply pathogenic IL-18 activity; the key translational question is whether IL-18BP-mediated restraint remains sufficient. In barrier disorders More >

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Gabriele Ricciardi^1,2,#,*, Mariagiovanna Ballato^1,#, Gabriele Di Carlo³, Domenico Donadio^1,2,4,5, Emanuela Germanà¹, Flavio Corpina^2,6,7, Carmela Lipari^2,6,8, Guido Fadda⁹, Danilo Leonetti³, Biagio Zampogna^3,4,5, Marco Ferlazzo², Maurizio Martini^9,*
European Cytokine Network, Vol.37, No.3, pp. 169-191, 2026, DOI:10.32604/ecn.2026.084855 - 28 September 2026
Abstract Osteoarthritis (OA) is increasingly recognized as a multifactorial disease in which metabolic dysfunction and chronic low-grade inflammation contribute to joint degeneration. Among the mediators involved, leptin has emerged as a key adipokine linking obesity, aging, and inflammatory processes to OA development and progression. However, despite growing evidence, its role remains incompletely understood, and a comprehensive framework integrating leptin-related mechanisms across different joint tissues is still lacking. This review provides an updated overview of the role of leptin in OA pathogenesis, focusing on its effects on cartilage, synovium, subchondral bone, and the infrapatellar fat pad. We… More >

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Paula Guerrero, M. Luisa Gil, Alberto Yáñez^*
European Cytokine Network, Vol.37, No.3, pp. 193-206, 2026, DOI:10.32604/ecn.2026.086544 - 28 September 2026
Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine classically recognized as a central regulator of emergency myelopoiesis, promoting the expansion and differentiation of hematopoietic stem and progenitor cells (HSPCs) towards the myeloid lineage during infection and inflammation. In addition, GM-CSF enhances myeloid cell recruitment and activation, boosting antimicrobial functions and inflammatory responses. This coordinated capacity to enhance myelopoiesis while amplifying effector functions reflects a broader property of GM-CSF to functionally reprogram the hematopoietic system, not only increasing myeloid output but also shaping the inflammatory potential of downstream myeloid cells. However, this enhanced potential must be More >

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REVIEW

Mihaela Andreescu^1,2, Laura Tirlea^1,3, Alina Tanase^3,4, Cosmin Alec Moldovan^1,5,*, Stefana Petrut⁶, Daniel Cochior^1,7, Adina-Diana Moldovan^6,8, Monica-Daniela Padurariu-Covit^9,10
European Cytokine Network, Vol.37, No.3, pp. 207-223, 2026, DOI:10.32604/ecn.2026.086087 - 28 September 2026
Abstract Accumulating evidence suggests that the gut microbiota regulates cytokine gene expression through multiple epigenetic mechanisms that shape chromatin states in response to microbial metabolites. Alterations in the gut microbiota have been implicated in the pathogenesis of numerous inflammatory, autoimmune, and metabolic disorders. Key mediators including short-chain fatty acids, bile acids, and tryptophan derivatives modulate histone modifications and DNA methylation at cytokine gene loci, influencing the balance between pro-inflammatory and tolerogenic immune responses. Experimental evidence, including ChIP-seq studies, indicates that microbial colonization promotes regulatory chromatin configurations, while dysbiosis is associated with epigenetic patterns favoring inflammatory cytokine More >

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Roberto Zefferino^1,*, Annalucia Carbone², Aglaja Zefferino², Sante Di Gioia², Massimo Conese^2,*
European Cytokine Network, Vol.37, No.3, pp. 225-248, 2026, DOI:10.32604/ecn.2026.079385 - 28 September 2026
Abstract Cancer and fibrosis are two pathological conditions that although of different clinical appearance have several shared characteristics, most likely because of a common etiology (for example in case of Silica). Here, we present a comprehensive review of the literature, with respect to Crystalline Silica, a known carcinogenic and fibrogenic agent, aiming to highlight common denominators between both diseases, as well as their differences. The results from various studies point to the involvement of the immune response, cancer-associated fibroblasts (CAFs), cellular communication and various signaling pathways, including Notch, Wnt/β-catenin, and YAP/TAZ in their respective pathogenesis. In More >

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Gaia Cicolani¹, Caterina Cocchi², Emanuela Anastasi^1,*
European Cytokine Network, Vol.37, No.3, pp. 249-257, 2026, DOI:10.32604/ecn.2026.088372 - 28 September 2026
Abstract Growth Differentiation Factor 15 (GDF15) is a stress-responsive cytokine linking metabolism, inflammation and disease pathophysiology. In this review, we provide a comprehensive overview of its physiological and pathological functions, emphasising its relevance in various clinical contexts. We discuss the molecular mechanisms that regulate its expression and signalling, its role as a systemic biomarker of cellular and mitochondrial stress, and its function in maintaining metabolic homeostasis and in obesity-related disorders. In oncology, this cytokine plays a pivotal role by displaying context-dependent functions as a mediator of tumour progression, immune modulation and cancer-associated cachexia, making it both More >

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Qi Song^1,2,3, Ming Li^1,2, Zhiliang Jin⁴, Han Zhang^1,2, Haisen Yin^1,2,*, Shiyun Tan^1,*, Baoping Yu^1,*
European Cytokine Network, Vol.37, No.3, pp. 259-280, 2026, DOI:10.32604/ecn.2026.084574 - 28 September 2026
（This article belongs to the Special Issue: Inflammation in Disease: When Cytokine Conversations Tell the Whole Story)
Abstract Short-chain fatty acids (SCFAs) are increasingly recognized as active modulators of tumor immunity. However, organizing evidence only by tumor type, metabolite species, or individual pathway may not fully explain their context-dependent effects. This Review clarifies how SCFAs regulate tumor immunity by remodeling cytokine and chemokine networks within the tumor microenvironment and defines the contextual factors that determine whether these effects support or restrain antitumor responses. We organize SCFA-driven effects into four functional cytokine domains: pro-inflammatory, antitumor effector, immunosuppressive, and chemotactic/angiogenic mediators. Across these domains, SCFAs act through inflammasome modulation, receptor-mediated signaling, epigenetic regulation, and metabolic More >

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Yan Zhu, Wenhao Zhang, Yunqiu Gao^*
European Cytokine Network, Vol.37, No.3, pp. 281-292, 2026, DOI:10.32604/ecn.2026.087229 - 28 September 2026
（This article belongs to the Special Issue: Targeting Non-Canonical Cytokine Sources in the Tumor Microenvironment: From Biology to Novel Antitumor Strategies)
Abstract Cellular senescence is a durable stress response with double effects on cancer. Although stable cell-cycle arrest may initially restrict tumor growth, senescent tumor and stromal cells remain metabolically active and can remodel the tumor microenvironment through the senescence-associated secretory phenotype (SASP). This review synthesizes current evidence on therapy-induced and tumor-intrinsic senescence in prostate, bladder, and kidney cancers, focusing on molecular regulation and context-dependent SASP effects. We discuss how NF-κB, JAK/STAT3, cGAS-STING, and p38 MAPK regulate SASP composition. These pathways help determine the composition of the SASP, including the cytokines, chemokines, growth factors, and matrix-remodeling enzymes More >

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Rajallectchumy Subramaniam, Nelli Giribabu^*, Naguib Salleh^*
European Cytokine Network, Vol.37, No.3, pp. 293-318, 2026, DOI:10.32604/ecn.2026.080872 - 28 September 2026
Abstract This narrative review summarises epidemiological associations and evaluates proposed mechanisms linking gout and hyperuricaemia with cardiovascular dysfunction and remodelling. Gout is a crystal arthropathy that is increasingly recognised as also carrying systemic cardio-inflammatory features. Hyperuricaemia and monosodium urate (MSU) crystals trigger Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome signalling, driving IL-1β, IL-6, and TNF-α release together with xanthine oxidase (XO)–derived oxidative stress. Experimental studies in hyperuricaemia and non-gout cardiovascular models suggest that these cascades contribute to endothelial dysfunction and promote cardiac fibroblasts through TGF-β/Smad, JAK2/STAT3/HMGCS2, and… More >

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Hitoshi Uga^1,*, Takahiro Okazawa¹, Yoshiaki Miyamoto¹, Takehiro Hasegawa¹, Jun Saegusa², Akio Morinobu^2,3, Shunichi Kumagai⁴, Hirokazu Kurata^1,5
European Cytokine Network, Vol.37, No.3, pp. 319-329, 2026, DOI:10.32604/ecn.2026.083162 - 28 September 2026
Abstract Background: Early and accurate differential diagnosis of rheumatoid arthritis (RA) remains challenging, particularly in patients with seronegative or non-specific inflammatory arthritides. Because cytokines and chemokines play central roles in immune activation and leukocyte trafficking, we investigated whether serum cytokine and chemokine profiles could discriminate RA from non-rheumatoid arthritides (NRA) and healthy controls (HCs). Methods: One hundred and fifty-seven RA patients (104 anti-cyclic citrullinated peptide antibody (ACPA)-positive and 53 ACPA-negative patients), 33 NRA patients and 86 HCs were included. Fourteen cytokines and twelve chemokines were measured in the sera of the above three cohorts, using high-sensitivity… More >

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Shengjie Xue^#, Shiyu Ni^#, Zehao Lan, Jieyue Liao^*
European Cytokine Network, Vol.37, No.3, pp. 331-348, 2026, DOI:10.32604/ecn.2026.086314 - 28 September 2026
（This article belongs to the Special Issue: Inflammation in Disease: When Cytokine Conversations Tell the Whole Story)
Abstract Background: Atopic dermatitis (AD) is associated with systemic immune dysregulation, but peripheral molecular markers that reliably reflect clinical severity remain insufficiently validated. Using complementary bulk and single-cell transcriptomics, we prioritized peripheral markers and evaluated them in independent clinical cohorts. Methods: Public peripheral blood mononuclear cell (PBMC) transcriptomes were analyzed by differential-expression analysis, weighted gene co-expression network analysis (WGCNA) with power-sensitivity and preservation assessments, immune-cell deconvolution, LASSO, and random forest. Descriptive single-gene receiver operating characteristic (ROC) curves summarized candidate discrimination in the discovery cohort. Selected transcripts were evaluated by RT-qPCR in a PBMC cohort, and serum… More >

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Ines Allam^1,2,#, Ouassila Madani^1,2,#, Brahim Belaid^1,2, Fatma Merah^1,2, Ferial Messaoui^3,4, Linda Azzoug^3,4, Abdelmalek Balamane^3,4, Reda Djidjik^1,2,*
European Cytokine Network, Vol.37, No.3, pp. 349-356, 2026, DOI:10.32604/ecn.2026.082748 - 28 September 2026
Abstract Background: Crohn’s disease (CD) is a chronic inflammatory disorder resulting from the interaction between genetic susceptibility, environmental factors, intestinal microbiota, and dysregulated immune responses. Despite major advances, the precise mechanisms underlying disease development remain incompletely understood. This study aimed to evaluate the proportions of Th17 and regulatory T (Treg) cells, as well as serum cytokine levels, in the peripheral blood of patients with CD. Methods: We enrolled 46 patients with active CD (median age: 31.5 years) and 30 healthy subjects (median age: 30.0 years). Th17 and Treg cell populations were analyzed by flow cytometry, while… More >

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