Journal of Inflammation Research最新文献

{"title":"Type 2 Inflammation in Asthma and COPD: Biomarkers, Clinical Applications, and Targeted Therapies.","authors":"Maosen Dou, Xue Zhang, Min Zhang","doi":"10.2147/JIR.S632705","DOIUrl":"https://doi.org/10.2147/JIR.S632705","url":null,"abstract":"<p><p>Type 2 (T2) inflammation is a major pathogenic pathway in asthma and a clinically relevant endotype in a subgroup of patients with chronic obstructive pulmonary disease (COPD). This narrative review compares the mechanisms, biomarker-based assessment, and targeted treatment of T2 inflammation across these diseases. We focus on blood and sputum eosinophils, fractional exhaled nitric oxide (FeNO), and total and allergen-specific immunoglobulin E (IgE), while examining discordance among biomarkers and the effects of corticosteroids, smoking, infection, circadian variation, coexisting T2 diseases, and population- or assay-dependent thresholds. We distinguish the adjunctive role of biomarkers in diagnosis from their more established roles in phenotyping, risk stratification, and treatment selection. Evidence from pivotal trials is synthesized for established and recently approved therapies, including the jurisdiction-specific positioning of depemokimab in severe asthma and mepolizumab in eosinophilic COPD, while investigational strategies targeting epithelial alarmins and related pathways are critically appraised. We also discuss clinical remission as an evolving treatment goal. Overall, repeated multidimensional assessment integrating biomarkers with clinical characteristics, lung function, comorbidities, exacerbation history, and treatment exposure is more informative than any single threshold and may support more precise management of asthma and COPD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"632705"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Non-Endoscopic Dynamic Nomogram for Atrophic Gastritis Risk Stratification Based on Serum Indicators and Clinical Factors.","authors":"Ziyi Fang, Yunjie Zhang","doi":"10.2147/JIR.S636426","DOIUrl":"https://doi.org/10.2147/JIR.S636426","url":null,"abstract":"<p><strong>Background: </strong>Atrophic gastritis (AG) is a key precancerous lesion in gastric carcinogenesis, underscoring the need for non-endoscopic screening tools to improve early detection. This study aimed to develop a predictive model for AG based on serum indicators and clinical factors.</p><p><strong>Methods: </strong>This single-center retrospective study enrolled 520 patients who underwent gastroscopy with biopsy at Shaoxing Second Hospital between January 2023 and December 2025. AG severity was classified via the Kimura-Takemoto system (no/mild: C0-C1, n=349; moderate/severe: C2-C3 and O-type, n=171). Multivariate analysis was performed to identify independent predictors. The performance of the resulting predictive model was evaluated, and decision curve analysis was used to evaluate the clinical utility across a range of threshold probabilities. An interactive dynamic nomogram was created for real-time risk calculation.</p><p><strong>Results: </strong>Multivariate analysis identified four independent predictors of moderate/severe AG: older age (OR = 1.082, P < 0.001), elevated neutrophil count (NE) (OR = 2.036, P = 0.043), decreased fibrinogen (FIB) (OR = 0.56, P < 0.001), and elevated carcinoembryonic antigen (CEA) (OR = 1.171, P = 0.011). The predictive model demonstrated good discrimination in the development cohort (AUC = 0.780) and was further evaluated in an independent 94-patient inter-campus cohort (AUC = 0.705), confirming its discriminatory ability within the same hospital system.</p><p><strong>Conclusion: </strong>This non-endoscopic model incorporating age, NE, FIB, and CEA provides a practical tool for AG risk stratification, As a single-center retrospective model, it requires further multi-center prospective validation before clinical implementation; nevertheless, it may help guide endoscopic surveillance decisions and contribute to the early prevention of gastric cancer.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"636426"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Firsekibart for the Treatment of Gout Complicated by Type 2 Diabetes Mellitus: A Real-World Case Series.","authors":"Mengjia Shen, Lin Zhu, Cheng Xu, Chen Zhu, Qiao Ye, Yongmei Han","doi":"10.2147/JIR.S639919","DOIUrl":"https://doi.org/10.2147/JIR.S639919","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"639919"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Growth Factor-β1 Drives Neutrophil Chemokinesis, Not Chemotaxis.","authors":"Louise E Crowley, Ellen Jenkins, Kirsty C McGee, Theodore S Smith, Jon Hazeldine, Robert A Stockley, David R Thickett, Dhruv Parekh, Aaron Scott","doi":"10.2147/JIR.S621030","DOIUrl":"https://doi.org/10.2147/JIR.S621030","url":null,"abstract":"<p><strong>Purpose: </strong>Idiopathic pulmonary fibrosis (IPF) is a devastating condition that is characterized by dysregulated repair responses to alveolar epithelial damage and progressive remodeling of the lung interstitium. Neutrophils are critical responders to tissue injury, but their role in organ fibrosis pathogenesis remains unclear. Neutrophil numbers are increased in bronchoalveolar spaces of IPF patients, and neutrophil activation markers are elevated in fibrotic lung tissue. However, the key mediators driving neutrophil movement in fibrotic lung diseases are unknown. Transforming growth factor-beta 1 (TGFβ1) is a critical pro-fibrotic cytokine, but its effect on neutrophil movement remains unclear. This mechanistic, exploratory study aimed to determine whether TGFβ1 alters neutrophil migration in a direction-dependent (chemotaxis) or direction-independent (chemokinesis) manner and to assess whether TGFβ1 exposure is accompanied by functional changes consistent with neutrophil priming.</p><p><strong>Methods: </strong>This study utilized human neutrophils from healthy donors to model aspects of a TGFβ1-rich environment. Neutrophil movement was assessed using a transwell migration assay and by real-time tracking of human neutrophils within an Insall chamber. Extracellular release of superoxide anions and nucleic acid were assessed by lucigenin-amplified chemiluminescence, and fluorometry, respectively. Expression of cell surface markers, TGFβ receptor 1 and pSmad2/3 were assessed using flow cytometry and Western blot.</p><p><strong>Results: </strong>This study revealed that TGFβ1 drives neutrophil chemokinesis, but not chemotaxis, and that pre-treatment with TGFβ1 amplified selected movement responses to the established chemoattractants, interleukin-8 and N-Formylmethionine-leucyl-phenylalanine. TGFβ1 also increased total superoxide anion production and nucleic acid release, but did not alter cell surface expression of adhesion (CD11b and CD62L) or degranulation (CD66b) markers.</p><p><strong>Conclusion: </strong>Together, these data suggest that TGFβ1 promotes neutrophil chemokinesis, rather than chemotaxis, and that this may reflect transition into a priming-like state with potential relevance to neutrophil behavior in conditions such as fibrotic lung disease.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"621030"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting IL-23p19 in Inflammatory Bowel Disease: The Road Ahead.","authors":"Erica Bartolotta, Giuseppe Privitera, Arianna Dal Buono, Roberto Gabbiadini, Laura Loy, Giulia Migliorisi, Cristina Bezzio, Alessandro Armuzzi","doi":"10.2147/JIR.S614998","DOIUrl":"https://doi.org/10.2147/JIR.S614998","url":null,"abstract":"<p><p>Selective interleukin-23p19 (IL-23p19) inhibition represents a major advance in the management of inflammatory bowel disease (IBD). Risankizumab, mirikizumab, and guselkumab - three monoclonal antibodies targeting the p19 subunit of IL-23 - have each completed Phase 3 clinical development programs in both Crohn's disease (CD) and ulcerative colitis (UC), demonstrating consistent efficacy across a broad spectrum of disease severity. Unlike ustekinumab, which blocks the shared p40 subunit of IL-12 and IL-23, selective p19 inhibition preserves IL-12-mediated host defense while more precisely targeting the IL-23/Th17 axis implicated in chronic intestinal inflammation. In phase 3 trials, all three agents significantly outperformed placebo for co-primary endpoints combining clinical remission and endoscopic response or remission, with benefits sustained across both induction and maintenance phases. Head-to-head data from the SEQUENCE trial demonstrate superiority of risankizumab over ustekinumab for endoscopic remission in CD, a finding corroborated by active comparator arms in GALAXI-2/3. Network meta-analyses consistently rank IL-23p19 inhibitors among the most effective therapies for moderate-to-severe CD. Real-world data, predominantly available for risankizumab in CD and mirikizumab in UC, confirm meaningful clinical and endoscopic responses in refractory populations, including patients with prior ustekinumab exposure. Safety profiles are favorable across indications, with no class-specific signals for serious infection, malignancy, or cardiovascular events. Approved indications for psoriasis and psoriatic arthritis (risankizumab and guselkumab) and pediatric psoriasis (guselkumab) offer additional therapeutic value for IBD patients with extraintestinal manifestations. Key evidence gaps persist, including the absence of head-to-head data in UC, limited long-term outcomes beyond 52 weeks, and the lack of validated predictive biomarkers for patient stratification. This narrative review synthesizes the biological rationale, clinical trial evidence, real-world data, and safety profiles, focusing on clinical positioning of IL-23p19 inhibitors in IBD in the context of precision medicine.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"614998"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Blood Eosinophils: Target-Tier Heterogeneity and Patient Enrichment in COPD Type 2 Inflammation.","authors":"Jinzhong Zhang, Peng Zhang, Yiyin Zhang, Yang Xie","doi":"10.2147/JIR.S626944","DOIUrl":"https://doi.org/10.2147/JIR.S626944","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) exhibits considerable clinical and biological heterogeneity, and frameworks centered on symptom burden, airflow limitation, and exacerbation risk do not fully explain variation in inflammatory pathways or responses to targeted therapies. Blood eosinophils (blood EOS) provide an accessible clinical biomarker for estimating inhaled corticosteroid (ICS) benefit, stratifying exacerbation risk, and enriching biologic trials in COPD. We position blood EOS as an entry biomarker within a target- and context-dependent framework because peripheral counts incompletely represent airway epithelial activation, local chemotaxis, mucus pathology, tissue EOS activation, or mixed inflammatory microenvironments. This focused narrative review integrates biologic trials, biomarker analyses, and human airway and lung-tissue studies to map type 2-related signals across target tiers. IL-5/IL-5R targeting tests the EOS effector-cell compartment. IL-4Rα blockade supports the therapeutic relevance of an IL-4/IL-13-associated epithelial-chemokine-tissue response program in selected enriched populations. IL-33/ST2 evidence supports therapeutic relevance in COPD, although efficacy remains intervention- and context-dependent, whereas TSLP evidence remains exploratory. Collectively, the evidence supports interpreting COPD type 2 inflammation through target tier, tissue pathway, and patient context. Future studies should test target-directed composite enrichment and prospectively link target perturbation, pathway readouts, and clinical responses.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"626944"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Local Expression of Interleukin-1β in Patients with Acute Myocardial Infarction with Local Layered Plaque.","authors":"Minghao Liu, Xing Luo, Xinxin Zhu, Qianhui Sun, Jianxin Huang, Dirui Zhang, Boling Yi, Ying Lv, Haibo Jia","doi":"10.2147/JIR.S597290","DOIUrl":"https://doi.org/10.2147/JIR.S597290","url":null,"abstract":"<p><strong>Background: </strong>Patients with acute myocardial infarction are found to have layered plaque in the culprit lesion site during optical coherence tomography, indicating that these patients have experienced recurrent thrombotic events locally. Whether inflammation factors are associated with this phenomenon remains unknown.</p><p><strong>Methods: </strong>A total of 125 patients with acute myocardial infarction who underwent coronary angiography followed by optical coherence tomography were prospectively enrolled. 17 patients were excluded due to various reasons. Peripheral blood samples were collected from all patients, and blood samples from the culprit vessel were collected during thrombus aspiration in a subset. All optical coherence tomography images of the culprit vessels were analyzed as well as quantitative coronary angiography. The mRNA expression of IL-1β, IL-4, IL-8, IL-10, IL-18, ELANE, MPO in monocytes of both peripheral and culprit lesion blood samples were analyzed.</p><p><strong>Results: </strong>Of the 108 eligible patients, 56 (51.9%) had layered plaque at the site of the culprit lesion. Clinical characteristics and quantitative coronary angiography showed no significant difference between the layered plaque and non-layered plaque groups. Layered plaque group had greater mean lipid arc (304.23° [284.52, 330.80] vs 288.16° [256.00, 311.00], <i>p</i>=0.047). Peripheral blood samples revealed no difference in any inflammatory factors expression, however, higher mRNA expression level of IL-1β in culprit lesion blood was observed in layered plaque group, with a mean difference of 1.81 (95% BCa CI [0.66, 3.10], <i>p</i> =0.023). Firth's penalized likelihood logistic regression analysis showed that mRNA expression level of IL-1β was significantly associated with layered plaque (OR, 1.78, 95% CI, 1.16-3.29, <i>p</i>=0.005) after adjusting for age and sex. ROC analysis demonstrated that IL-1β yielded an AUC of 0.781 (95% CI: 0.637-0.924) for predicting layered plaque.</p><p><strong>Conclusion: </strong>IL-1β was expressed more in the culprit vessel in patients whose culprit lesion showed layered plaque, proving that local IL-1β is associated with layered plaque.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"597290"},"PeriodicalIF":4.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and Molecular Mechanisms of Vascular Endothelial Injury Induced by Cigarette Smoke and Cigarette Smoke Extract in Atherosclerosis.","authors":"Xiangjun Chen, Xinran Yang, Zhihan Li, Xin Sheng","doi":"10.2147/JIR.S627144","DOIUrl":"https://doi.org/10.2147/JIR.S627144","url":null,"abstract":"<p><p>Although smoking is a well-recognized independent risk factor for atherosclerosis (AS), its core pathogenic mechanism lies in the induction of vascular endothelial cell (VEC) dysfunction, which represents the initial step of AS development. However, the mechanisms by which cigarette smoke (CS) and cigarette smoke extract (CSE) trigger and promote atherosclerotic progression via VECs remain incompletely understood. CS and CSE damage the vascular endothelial barrier through three key mechanisms: oxidative stress induction, inflammatory response activation, and endothelial cell apoptosis. This narrative review summarizes the cellular and molecular mechanisms by which CS and CSE disrupt vascular endothelial cell function through activation of the nuclear factor kappa B (NF-κB) signaling pathway, the nitric oxide (NO) synthesis pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway, based on experimental studies at the cellular and organ levels. This review aims to provide a novel perspective for clarifying the pathological basis of smoking-induced atherosclerosis and lay a foundation for the development of intervention strategies targeting endothelial protection.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"627144"},"PeriodicalIF":4.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formononetin Protects Against Cerebral Ischemia-Reperfusion-Induced Lung Injury: Insights from Animal and Cell Models.","authors":"Luying Chen, Yajie Zhou, Dan Yan, Lingyun Lou, Renzhi Zhou, Huijun Chen, Saibin Wang","doi":"10.2147/JIR.S608652","DOIUrl":"https://doi.org/10.2147/JIR.S608652","url":null,"abstract":"<p><strong>Background: </strong>Cerebral ischemia-reperfusion (CIR) affects multiple organs, with lung injury being particularly prevalent. Formononetin, derived from legumes, has multiple pharmacological effects and demonstrated potential for the treatment of neurological diseases. However, its effects on CIR-induced lung injury are unknown.</p><p><strong>Objective: </strong>To investigate the protective effect of formononetin in CIR-induced lung injury (in the Sprague-Dawley (SD) rats' model).</p><p><strong>Methods: </strong>Sprague-Dawley rats (n=27) underwent middle cerebral artery occlusion (MCAO) to establish a CIR model. Formononetin was then administered at specific time points. Longa neurological deficit score, histological staining, enzyme-linked immunosorbent assay (ELISA), and flow cytometry were subsequently used to assess lung injury. In addition, rat microglia were exposed to oxygen-glucose deprivation/re-oxygenation (OGD/R) to mimic CIR in vitro, and exosomes were then extracted from these cells for testing. A lipopolysaccharide (LPS)-induced lung epithelial cell injury model was subsequently used to investigate the protective effects of formononetin.</p><p><strong>Results: </strong>ELISA revealed that formononetin exerted broad-spectrum anti-inflammatory effects, reducing TNF-α, IL-1β, IL-6, and IL-10 by 46.7%, 46.2%, 40.1%, and 54.6%, respectively, in bronchoalveolar lavage fluid after MCAO (P<0.05). In lung tissues, superoxide dismutase (SOD) expression was increased, while malondialdehyde (MDA) was decreased (22.8%). Additionally, formononetin reduced interferon-gamma positive (INF-γ⁺), IL-4⁺, IL-17A⁺, forkhead box P3 protein positive (Foxp3⁺), cluster of differentiation 4 positive (CD4⁺), and CD8⁺ by 72.3%, 76.7%, 66.1%, 67.7%, 78.4%, and 80.4%, respectively, all to sham levels (P < 0.05). The in vitro experiments also revealed a downward trend in the expression of inflammatory factors in lung epithelial cells, with increased SOD expression (26.2%) and decreased MDA levels (21.7%, P<0.05).</p><p><strong>Conclusion: </strong>Formononetin protects against lung injury by inhibiting inflammatory cytokines, reducing oxidative stress, and regulating immune cells. Notably, exosomes derived from formononetin-treated microglia were shown to attenuate LPS-induced lung epithelial cell injury, highlighting a novel intercellular communication pathway. Together, these in vivo and in vitro studies offer new insights into the clinical application of formononetin in cerebrovascular diseases for secondary lung injury.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"608652"},"PeriodicalIF":4.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Mast Cells and Their Potential as a Therapeutic Target For Neuroinflammation.","authors":"Sarah Adriana Scuderi, Rossella Basilotta, Laura Cucinotta, Alessio Ardizzone, Emanuela Esposito","doi":"10.2147/JIR.S540890","DOIUrl":"https://doi.org/10.2147/JIR.S540890","url":null,"abstract":"<p><p>Neuroinflammation is increasingly recognized as a central mechanism underlying the onset and progression of numerous neurological disorders, including neurodegenerative, autoimmune, and cerebrovascular diseases. Although microglia and astrocytes are traditionally considered the primary mediators of inflammatory responses within the central nervous system (CNS), accumulating evidence has identified mast cells (MCs) as important contributors to neuroimmune regulation. Strategically located at the interface between the peripheral immune system and the CNS, MCs can rapidly respond to a variety of endogenous and exogenous stimuli through the release of bioactive mediators, including histamine, proteases, cytokines, chemokines, and lipid-derived molecules. These mediators influence blood-brain barrier (BBB) integrity, promote glial activation, modulate neuronal signaling, and contribute to the amplification of inflammatory cascades. Increasing experimental and clinical evidence supports the involvement of MCs in the pathogenesis of several neurological conditions, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, migraine, and ischemic brain injury. Consequently, modulation of mast cell activity has emerged as a promising therapeutic approach for limiting neuroinflammatory damage and restoring neuroimmune homeostasis. This review provides an overview of mast cell biology within the CNS, discusses the molecular mechanisms linking MCs to neuroinflammation, examines their contribution to major neurological disorders, and highlights current and emerging therapeutic strategies targeting MCs-mediated pathways. A deeper understanding of mast cell functions in neuroinflammatory processes may facilitate the development of innovative and more effective interventions for neurological diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"540890"},"PeriodicalIF":4.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}