Cytokine最新文献

{"title":"Fluoxetine mitigates hypothermia and inflammatory responses in lipopolysaccharide-induced systemic inflammation: Insights into serotonergic and hypothalamic thermoregulatory mechanisms","authors":"Isis P. Trajano ,&nbsp;Luis Henrique Angenendt Costa ,&nbsp;Patrícia Passaglia ,&nbsp;Wanderson S. Santos ,&nbsp;Jonathas Rodrigo dos Santos ,&nbsp;Luciane Carla Alberici ,&nbsp;Luiz G.S. Branco","doi":"10.1016/j.cyto.2025.156909","DOIUrl":"10.1016/j.cyto.2025.156909","url":null,"abstract":"<div><div>An abnormally elevated mortality rate is evident in cases of sepsis. To study specific mechanisms of sepsis experimentally, lipopolysaccharide (LPS) systemically administered has been used as a model, in which an exaggerated immune response, neurochemistry settings, and fever following hypothermia take place. Notably, systemic inflammation (SI) can modulate the central serotonergic pathways and being influenced by it. This influence extends to the hypothalamus, which holds a hierarchical significance in the control of body temperature (Tb). This study investigates the potential impact of orally administered fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) given orally for 7 days before on LPS-induced SI (1.5 mg/kg, i.v.) in rats. The assessment involved monitoring Tb, heat loss index (HLI), along non-shivering thermogenesis assessed by oxygen consumption. Cytokine levels in the spleen and blood, along with nitric oxide (NO), and prostaglandins (PGs) E₂ and D_2, levels were also measured. The findings reveal increased plasma NO, cytokines in plasma and spleen, and hypothalamus PGE₂ levels during SI. Interestingly, FLX mitigated LPS-induced hypothermia, accompanied by a reduction in plasma and splenic NO, interleukins (IL) 6, and 10. Additionally, the results align with the hypothesis that hypothermia, blunted by FLX, develops in fact in a regulated form, as an adaptive strategy.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156909"},"PeriodicalIF":3.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between serum levels of inflammatory mediators and periodontitis severity in people with down syndrome","authors":"Katia M.M. Veloso ,&nbsp;Monique M.M. Mouchrek ,&nbsp;Joana A.B. de Sousa ,&nbsp;Cecília C.C. Ribeiro ,&nbsp;Vandilson P. Rodrigues ,&nbsp;Bruno B. Benatti","doi":"10.1016/j.cyto.2025.156910","DOIUrl":"10.1016/j.cyto.2025.156910","url":null,"abstract":"<div><div>Evidence suggests that individuals with Down syndrome (DS) have a high prevalence of periodontal disease (PD). Factors such as muscular hypotonia, macroglossia, intellectual deficits, and reduced motor coordination, often combined with inadequate dietary habits, contribute to the development of PD. Additionally, a compromised immune response may explain the altered inflammatory profile that affects the systemic and oral health of this population. This study aimed to analyze the relationship between serum levels of inflammatory cytokines (IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α) and the severity of periodontitis in individuals with DS. We conducted a case-control study involving individuals with DS (<em>n</em> = 43) and non-syndromic individuals (<em>n</em> = 20). All participants underwent a clinical periodontal examination that included measurements of probing pocket depth (PPD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Participants were classified into stages of periodontitis: stage 1 and stages 2–4, forming two subgroups within both the case and control groups. Serum levels of IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α were compared between subgroups and analyzed as continuous variables for independent samples. We compared the four subgroups while considering the stage of periodontitis and the presence of DS. The relationship between DS and the stages 2–4 periodontitis with inflammatory marker levels was analyzed using linear regression models, adjusted for age and sex. The results showed no association between periodontitis severity and serum cytokine levels in any of the subgroups (<em>P</em> &gt; 0.05). However, DS was associated with reduced serum levels of IFN-γ and increased serum levels of IL-10, IL-1β, IL-4, and TNF-α (<em>P</em> &lt; 0.05). These findings suggest that individuals with DS have increased serum levels of inflammatory cytokines compared to non-syndromic individuals, regardless of the severity of periodontitis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156910"},"PeriodicalIF":3.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of VEGF in Cancer angiogenesis and tumorigenesis: Insights for anti-VEGF therapy","authors":"Zijun Shi ,&nbsp;Mengmeng Kuai ,&nbsp;Baohua Li ,&nbsp;Carlos Frimpong Akowuah ,&nbsp;Zhenyu Wang ,&nbsp;Ye Pan ,&nbsp;Min Tang ,&nbsp;Xiaoyue Yang ,&nbsp;Peng Lü","doi":"10.1016/j.cyto.2025.156908","DOIUrl":"10.1016/j.cyto.2025.156908","url":null,"abstract":"<div><div>Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis, playing a pivotal role in both physiological and pathological processes. It promotes the formation of new blood vessels and activates downstream signaling pathways that regulate endothelial cell function. This review highlights recent advancements in the understanding of VEGF's molecular structure and its isoforms, as well as their implications in disease progression. It also explores the mechanisms of VEGF inhibitors. While VEGF inhibitors show promise in the treatment of cancer and other diseases, their clinical use faces significant challenges, including drug resistance, side effects, and complex interactions with other signaling pathways. To address these challenges, future research should focus on: (i) enhancing the understanding of VEGF subtypes and their distinct roles in various diseases, supporting the development of personalized treatment strategies; (ii) developing combination therapies that integrate VEGF inhibitors with other targeted treatments to overcome resistance and improve efficacy; (iii) optimizing drug delivery systems to reduce off-target effects and enhance therapeutic outcomes. These approaches aim to improve the effectiveness and safety of VEGF-targeted therapies, offering new possibilities for the treatment of VEGF-related diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156908"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The restoration of immunity characterized by the recovery of myeloid dendritic cells represent a favorable response to methylprednisolone therapy for HBV-ACLF patients: A prospective cohort study","authors":"Lin Jia ,&nbsp;Wei-Ping He ,&nbsp;Hui-Chun Xing ,&nbsp;Juan Li ,&nbsp;Hong-Wei Yu ,&nbsp;Wei Hou ,&nbsp;Ran Xue ,&nbsp;Juan Zhao ,&nbsp;Qing-Hua Meng","doi":"10.1016/j.cyto.2025.156894","DOIUrl":"10.1016/j.cyto.2025.156894","url":null,"abstract":"<div><h3>Background</h3><div>The use of methylprednisolone (MP) is still controversial for hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). We aimed to explore the change in dendritic cells (DCs) during MP treatment in HBV-ACLF to guide the use of MP to improve patient's prognosis.</div></div><div><h3>Methods</h3><div>Patients with HBV-ACLF were prospectively allocated to groups given methylprednisolone intravenously (1.5 mg/kg/day for the first 3 days, 1 mg/kg/day for the second 2 days, and 0.5 mg/kg/day for the last 2 days, MP group, <em>n</em> = 36) plus standard treatment or standard treatment only (CM group, <em>n</em> = 34). The phenotype [myeloid and plasmacytoid DCs (mDCs, pDCs)] and function of DCs (IL-12 and IFN-α production) were measured at baseline (0d), 3d, 7d, 10d, 14d, 28d, and then monthly until 3 months. Patients' survival was assessed until day 90.</div></div><div><h3>Results</h3><div>The 3-month survival rate was significantly higher in the MP group than the control (72.0 % vs. 35.5 %，<em>P</em> &lt; 0.01). The phenotype and function of DCs were suppressed in the MP group. The mDCs counts was lower in non-survivors compared to survivors at baseline. Patients with a decline in mDCs counts at the 7th day and a continuous increase in mDCs counts from the 10th day presented a better outcome for patients with MP treatment. Bilirubin was the only relative factor for the restoration of mDCs in the MP group (odds ratio, 0.991; 95 % confidence interval, 0.984–0.999; <em>P</em> = 0.023).</div></div><div><h3>Conclusions</h3><div>Methylprednisolone could improve the outcome of HBV-ACLF by inhibiting the circulating mDCs counts. And the recovery of mDCs counts after methylprednisolone treatment could represent a favorable response. We can consider monitoring the circulating DCs counts to guide the use of MP in HBV-ACLF in order to improve patient outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156894"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic liposomes encapsulating IL-2 selectively induce apoptosis and significantly reduce the secretion of cytokines on M1-murine polarized macrophages","authors":"C.A. Vargas-Ángeles ,&nbsp;L. Trujillo-Cirilo ,&nbsp;E. Sierra-Mondragón ,&nbsp;R. Rangel-Corona ,&nbsp;B. Weiss-Steider","doi":"10.1016/j.cyto.2025.156903","DOIUrl":"10.1016/j.cyto.2025.156903","url":null,"abstract":"<div><div>Inflammatory diseases pose a global challenge due to the critical role of macrophages in their pathogenesis. This study evaluated the effects of cationic liposomes encapsulating IL-2 (LIP-IL-2) on murine peritoneal macrophages (MP) polarized towards M1 and M2 phenotypes. M1 MP (CD86⁺), which overexpressed IL-2Rα and CD14 receptors, underwent apoptosis following LIP-IL-2 treatment, whereas M2 MP (CD206⁺) were unaffected. Furthermore, LIP-IL-2 significantly reduced the secretion of pro-inflammatory cytokines, including IL-6, TNF-α, IFN-γ, and IL-12, exclusively in M1 macrophages. These findings suggest that LIP-IL-2 could serve as a promising therapeutic tool for chronic inflammatory diseases by selectively inducing apoptosis in pro-inflammatory M1 macrophages without affecting M2 ones, opening avenues for targeted therapies in diseases where chronic macrophage-mediated inflammation is a key factor.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156903"},"PeriodicalIF":3.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAA1 as a key mediator of immune inflammatory pathways in fungal keratitis through FOXO3a phosphorylation regulation","authors":"Yihe Liu ,&nbsp;Jing Hong ,&nbsp;Rongmei Peng","doi":"10.1016/j.cyto.2025.156898","DOIUrl":"10.1016/j.cyto.2025.156898","url":null,"abstract":"<div><h3>Objective</h3><div>Fungal keratitis (FK) is a severe ocular infection, with its underlying molecular mechanisms remaining incompletely understood. This study aimed to identify and investigate key genes involved in immune-inflammatory responses associated with FK pathogenesis using bioinformatics and in vitro assays.</div></div><div><h3>Methods</h3><div>Transcriptomic data from the Gene Expression Omnibus (GEO) database (GSE58291) were analyzed using the limma package to identify differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to evaluate significant biological processes and pathways related to DEGs. Weighted gene co-expression network analysis (WGCNA) identified gene modules linked with FK-associated DEGs, and Venn diagram analysis highlighted core genes. Receiver operating characteristic (ROC) analysis assessed diagnostic potential. Immune cell composition was analyzed using CIBERSORT, and correlations between key genes and immune cells were evaluated. In vitro, human corneal epithelial cells (HCEC) were stimulated with <em>Aspergillus fumigatus (A.F.)</em>, and pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) was assessed using enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyzed FOXO3a phosphorylation and gene expression changes post-SAA1 siRNA transfection.</div></div><div><h3>Results</h3><div>A total of 101 DEGs were identified, with WGCNA revealing 6 co-expression network modules, with significant associations noted in yellow and black modules. Nine shared genes were identified in DEGs and modules, with SAA1 strongly linked to FK pathogenesis. SAA1 expression was positively correlated with neutrophils, T cells CD4 memory activated, T cells gamma delta, and activated mast cells. Upon stimulation with <em>A.F.</em>, cytokine expression increased, peaking at 24 h. Inhibition of SAA1 reduced FOXO3a phosphorylation and pro-inflammatory cytokine levels, underscoring SAA1's role in FK inflammation via FOXO3a regulation.</div></div><div><h3>Conclusion</h3><div>SAA1 is a key gene in FK, promoting inflammation by modulating FOXO3a phosphorylation. This highlights its potential as a therapeutic target in managing FK-related inflammation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156898"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine atlas of the population-based cohort SHIP-TREND-0 – Associations with age, sex, and BMI","authors":"Sabine Ameling ,&nbsp;Sandra Van der Auwera ,&nbsp;Silva Holtfreter ,&nbsp;Anja Wiechert ,&nbsp;Stephan Michalik ,&nbsp;Nele Friedrich ,&nbsp;Elke Hammer ,&nbsp;Henry Völzke ,&nbsp;Matthias Nauck ,&nbsp;Hans J. Grabe ,&nbsp;Barbara M. Bröker ,&nbsp;Uwe Völker","doi":"10.1016/j.cyto.2025.156896","DOIUrl":"10.1016/j.cyto.2025.156896","url":null,"abstract":"<div><h3>Background</h3><div>The characterization of physiological immune signatures in a population-based cohort is a prerequisite for identifying pathological immune signatures associated with inflammatory or autoimmune diseases.</div></div><div><h3>Methods</h3><div>Here, 47 plasma cytokines, chemokines, and growth factors were quantified with a bead-based multiplex-assay (Merck HCYTA-60 K) using a FLEXMAP 3D™ instrument in 1175 individuals of the Study of Health in Pomerania (SHIP; TREND cohort, 532 men and 643 women, age: 20 to 81, BMI: 17.7 to 53.6). Associations of cytokine concentrations with age, sex, BMI, season, and blood cell parameters (BCP) were examined by multivariate regression models.</div></div><div><h3>Results</h3><div>The physiological cytokine concentrations differed strongly between analytes, with median concentrations ranging from 0.6 to 7820 pg/mL. Many cytokine levels showed a large dynamic range within the study population. Higher levels of the pro-inflammatory cytokines and chemokines IL-6, IL-8, CXCL9, CXCL10, IL-12p40, CCL2, CCL4, CCL11, IL-27, FLT3LG, and TNFα were significantly associated with increasing age. The strongest age-associated effects were seen for CXCL9 (β_st = 0.4, <em>p</em> &lt; 0.001) and CXLC10 (β_st = 0.3, p &lt; 0.001). Significant sex differences were detected for CCL2, CCL3, CCL4, CCL11, CCL22, IL-12p40, IL-1RA, IL-18, IL-27, and TNFα levels among which CCL11 showed the strongest effect (β_st = −0.24, <em>p</em> &lt; 0.001) with a lower level in women compared to men. Moreover, seven cytokines and chemokines, i.e. CCL4, CCL22, CXCL10, IL-1RA, IL-18, IL-6, and TNFα, displayed higher levels with increasing BMI. Among those, the strongest effect was seen for IL-1RA (β_st = 0.19, <em>p</em> &lt; 0.001), CCL4 (β_st = 0.16, p &lt; 0.001) and CXCL10 (β_st = 0.14, p &lt; 0.001). Only CCL11 (β_st = −0.17, p &lt; 0.001) decreased with increasing BMI. Subjects categorized as obese exhibited significantly elevated levels of CCL4, CCL22, CXCL10, and IL-1RA, while only CCL11 showed significantly reduced levels compared to normal weight. Certain cytokines such as IL-6, IL-18, or TNFα showed decreased significance levels after adjustment for blood cell components indicating blood cell components (BCPs) as potential confounders. We observed no significant non-linear seasonal effects for the investigated cytokines.</div></div><div><h3>Conclusion</h3><div>The generated cytokine atlas provides detailed information on cytokine variations in the general population and will provide a reference base for disease-related studies in the future. Furthermore, BCPs should be considered as potential confounders in association studies based on plasma cytokine levels.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156896"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of cytokines in shaping the future of Cancer immunotherapy","authors":"Sahar Safaei ,&nbsp;AmirHossein Yari ,&nbsp;Omid Pourbagherian ,&nbsp;Leili Aghebati Maleki","doi":"10.1016/j.cyto.2025.156888","DOIUrl":"10.1016/j.cyto.2025.156888","url":null,"abstract":"<div><div>As essential immune system regulators, cytokines are essential for modulating both innate and adaptive immunological responses. They have become important tools in cancer immunotherapy, improving the immune system's capacity to identify and destroy tumor cells. This article examines the background, workings, and therapeutic uses of cytokines, such as interleukins, interferons, and granulocyte-macropHage colony-stimulating factors, in the management of cancer. It examines the many ways that cytokines affect immune cell activation, signaling pathways, tumor development, metastasis, and prognosis by modifying the tumor microenvironment. Despite the limited effectiveness of cytokine-based monotherapy, recent developments have concentrated on new fusion molecules such as immunocytokines, cytokine delivery improvements, and combination techniques to maximize treatment efficacy while reducing adverse effects. Current FDA-approved cytokine therapeutics and clinical trial results are also included in this study, which offers insights into how cytokines might be used with other therapies including checkpoint inhibitors, chemotherapy, and radiation therapy to address cancer treatment obstacles. This study addresses the intricacies of cytokine interactions in the tumor microenvironment, highlighting the possibility for innovative treatment methods and suggesting fresh techniques for enhancing cytokine-based immunotherapies. PEGylation, viral vector-mediated cytokine gene transfer, antibody-cytokine fusion proteins (immunocytokines), and other innovative cytokine delivery techniques are among the novelties of this work, which focuses on the most recent developments in cytokine-based immunotherapy. Additionally, the study offers a thorough examination of the little-reviewed topic of cytokine usage in conjunction with other treatment techniques. It also discusses the most recent clinical studies and FDA-approved therapies, providing a modern perspective on the developing field of cancer immunotherapy and suggesting creative ways to improve treatment effectiveness while lowering toxicity.</div></div><div><h3>Background</h3><div>Cytokines are crucial in cancer immunotherapy for regulating immune responses and modifying the tumor microenvironment (TME). However, challenges with efficacy and safety have driven research into advanced delivery methods and combination therapies to enhance their therapeutic potential.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156888"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of inflammation by IL-6 blockade in xenotransplantation","authors":"Zuzanna Iwanczyk ,&nbsp;Hidetaka Hara ,&nbsp;David K.C. Cooper ,&nbsp;Akihiro Maenaka","doi":"10.1016/j.cyto.2025.156897","DOIUrl":"10.1016/j.cyto.2025.156897","url":null,"abstract":"<div><div>The inflammatory cytokine interleukin 6 (IL-6) plays a role in both acute and chronic organ allotransplant rejection. Data suggest that IL-6 inhibition may help prevent or reverse rejection, with large multi-center trials now underway. However, the evidence for the benefit of IL-6 inhibitors in xenotransplantation is limited. IL-6 inhibition has been explored in nonhuman-primate models of xenotransplantation, but no clear consensus exists on its efficacy or the best mode of IL-6 inhibition (anti-IL-6 antibodies, or through IL-6 receptor [IL-6R] blockade).</div><div>Extra considerations for IL-6 blockade exist in xenotransplantation, as both recipient (human) and xenograft-derived (porcine) IL-6 may play roles. The systemic inflammation seen in xenograft recipients (SIXR) contributes to significant morbidity and mortality for the recipient through coagulation dysfunction and augmentation of the immune response. Anti-IL-6 antibodies (e.g., siltuximab) bind to human IL-6 and prevent IL-6R activation, but do not bind to porcine IL-6, and so have no effect in preventing graft-driven inflammatory processes. In contrast, IL-6R inhibitors (e.g., tocilizumab) inhibit IL-6 activity by blocking binding of human and porcine IL-6 to human IL-6R. Although IL-6R blockade cannot prevent the effect of IL-6 on porcine cells, it probably prevents graft-derived IL-6 from contributing to an inflammatory response in the host.</div><div>This review outlines the role of IL-6 in xenotransplantation and discusses mechanisms for inhibiting IL-6 to improve recipient survival.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156897"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the evidence for GM-CSF as a host-directed therapy in respiratory infections","authors":"Camille David ,&nbsp;Charles Verney ,&nbsp;Mustapha Si-Tahar ,&nbsp;Antoine Guillon","doi":"10.1016/j.cyto.2025.156902","DOIUrl":"10.1016/j.cyto.2025.156902","url":null,"abstract":"<div><div>Novel therapeutic approaches are needed to treat respiratory infections due to the rising antimicrobial resistance and the lack of effective antiviral therapies. A promising avenue to overcome treatment failure is to develop strategies that target the host immune response rather than the pathogen itself. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in controlling homeostasis in lungs, alveolar macrophages being the most sensitive cells to GM-CSF signaling. In this review, we discuss the importance of GM-CSF secretion for lung homeostasis and its alteration during respiratory infections. We also present the pre-clinical evidence and clinical investigations evaluating GM-CSF-based treatments (administration or inhibition) as a therapeutic strategy for treating respiratory infections, highlighting both supporting and contradictory findings.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156902"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}