Journal of Interferon and Cytokine Research最新文献

{"title":"Genetic Profiling of Interleukin Variants and their Correlation with Hepatitis C Viral Response to Different Therapeutic Strategies Administered in Pakistani Patients.","authors":"Izza Taufiq, Humera Naveed, Iram Amin, Muhammad Shahid, Muhammad Idrees, Samia Afzal","doi":"10.1177/10799907261438862","DOIUrl":"10.1177/10799907261438862","url":null,"abstract":"<p><p>This research study aimed to investigate the response of patients infected with the hepatitis C virus (HCV) toward direct-acting antivirals (DAAs) therapy. The research included a cohort of HCV-infected patients from different regions of Pakistan. Experimental studies were performed for the detailed analysis of virological response recorded at specific time intervals during the whole course of treatment. Sustained virological response (SVR) was explicitly defined as undetectable HCV RNA at 12 weeks post-completion of therapy (SVR12), ensuring alignment with international clinical standards. The standard genotypes analyzed for the selected interleukin (IL) variants were: IL-4 rs2243250 (C/C, C/T, T/T), IL-17 rs612242 (A/A, A/G, G/G), and IL-22 rs2064501 (A/A, A/G, G/G). The genetic profiling of these variants highlighted the significant role of cytokines in modulating the patient's immune response. The research also focused on the association between single-nucleotide polymorphisms (SNPs) of IL genes and categorization based on the outcomes of treatment by sequencing analysis. Our study found that the IL-4 rs2243250 SNP was predominantly heterozygous as CT in 52% SVR and 37% relapse patients. The IL-17 rs612242 SNP was mainly identified as AG in 54% SVR and 39% relapse patients, and the IL-22 rs2064501 SNP was prevalent in 32% relapse and 49% SVR patients as AG genotype. A homozygous genotype T/T was also analyzed for polymorphism rs2243250 in a relatively small percentage (16%) of non-responders. These research findings showed that C/T, C/C, and A/G genotypes were dominant in patients who cleared the infection after treatment. It confirmed the influence of single-nucleotide polymorphisms on the success rate of DAAs therapy, determined by observing the baseline characteristics and genetic factors of selected patients after comparing with healthy controls. Due to the limited genotyping of healthy controls (<i>n</i> = 4), comparative results involving the control group were interpreted with caution.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 6","pages":"153-162"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Interleukin 17 Polymorphisms and IL17A Levels with Papillary Thyroid Carcinoma: A Hospital-Based Study in the Chinese Population.","authors":"Sijie Yao, Kebin Lu, Tianxiang Wang","doi":"10.1177/10799907261438896","DOIUrl":"10.1177/10799907261438896","url":null,"abstract":"<p><p>Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, and inflammation and immune dysregulation contribute to its pathogenesis. Interleukin (IL)17A's role has been demonstrated in PTC. Genetic variants in IL17A may affect susceptibility and progression; however, their impact in the Chinese population remains insufficiently understood. This hospital-based case-control study included 272 patients with PTC and 250 age/sex-matched controls. Four IL17A single-nucleotide polymorphisms-rs2275913, rs3748067, rs8193036, and rs3819024-were genotyped using TaqMan assays. IL17A plasma levels were measured by ELISA. Allele, genotype, and haplotype distribution among controls and patients, and IL17 variant associations with IL17A levels were analyzed using GraphPad Prism. The rs2275913 AA genotype and minor allele showed a higher frequency in patients with PTC compared to controls, indicating an increased risk of PTC (AA: odds ratio [OR] = 1.88, 95% confidence intervals [CI] = 1.17-2.95, <i>P</i> = 0.01; A: OR = 1.44, 95% CI = 1.12-1.84, <i>P</i> = 0.003). Patients with PTC had higher plasma IL17A levels than controls (<i>P</i> < 0.0001). IL17A genotypes, particularly rs2275913 AA, were associated with higher plasma IL17A concentrations. Genetic polymorphisms in IL17A (rs2275913) and elevated plasma IL17A levels correlate with PTC susceptibility in the Chinese cohort. These findings suggest IL17A's potential as a biomarker for risk stratification and highlight inflammatory pathways in PTC pathogenesis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 6","pages":"163-170"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>RAB5A</i> Governs Synovial Fibroblast Extracellular Vesicles and Mediates Chondrocyte Degeneration in Osteoarthritis.","authors":"Zhenxing Zhang, Yangchun Wu, Xiongfei Tang, Zhigang Liu, Xuan'ang Yang, Zhen Ge","doi":"10.1177/10799907261435767","DOIUrl":"10.1177/10799907261435767","url":null,"abstract":"<p><p>Osteoarthritis is a degenerative joint disease characterized by synovial inflammation and cartilage destruction. This study aimed to investigate the function of <i>RAB5A</i> in regulating human fibroblast-like synoviocytes (HFLS) and its subsequent impact on chondrocyte degeneration. Differential expression and pathway analyses were performed according to the Gene Expression Omnibus (GEO) dataset. HFLS were stimulated with IL-1β, and <i>RAB5A</i> was knocked down via transfection. Inflammatory signaling, cytokine expression, and extracellular vesicles (EVs) secretion were assessed. Isolated EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. The functional effects of HFLS-derived EVs on chondrocyte inflammation, extracellular matrix metabolism, apoptosis, and viability were evaluated. Bioinformatics analysis identified <i>RAB5A</i> as a key gene linked to the endocytosis pathway. In IL-1β-stimulated HFLS, <i>RAB5A</i> expression was upregulated. <i>RAB5A</i> knockdown reduced the activation of p38 and NF-κB pathways and suppressed pro-inflammatory factors and matrix degradation mediators. Furthermore, <i>RAB5A</i> deficiency impaired EV secretion and altered their cargo. Crucially, while EVs from control HFLS promoted chondrocyte catabolism, inflammation, and apoptosis, EVs from <i>RAB5A</i>-knockdown HFLS mitigated these degenerative phenotypes. Our findings demonstrate that <i>RAB5A</i>, by modulating the biogenesis and composition of HFLS-derived EVs, plays a critical role in driving chondrocyte degeneration, highlighting its importance as a key molecular regulator in osteoarthritis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 6","pages":"171-180"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor-18 (FGF-18) Attenuates ox-LDL-Induced Endothelial Inflammation and Monocyte Adhesion by Inhibiting TRIM28.","authors":"Chaojuan Yuan, Zhongling Liu, Wenjuan Ye, Hong Ding","doi":"10.1177/10799907261432943","DOIUrl":"10.1177/10799907261432943","url":null,"abstract":"<p><p>The adhesion of monocytes to vascular endothelial cells constitutes a fundamental early process in atherogenesis. Fibroblast growth factor-18 (FGF-18), known to signal through the fibroblast growth factor receptor 1 (FGFR1), has emerging roles in maintaining vascular homeostasis, but its precise function in endothelial inflammation remains unclear. The protective role of recombinant human FGF-18 (rhFGF-18) against oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury and its mechanism were investigated. We found that ox-LDL downregulated phospho-FGFR1 in human aortic vascular endothelial cells (HAVECs) dose- and time-dependently. rhFGF-18 treatment markedly suppressed ox-LDL-induced upregulation of the scavenger receptor LOX-1 and key pro-inflammatory factors (TNF-α, MCP-1, COX-2, and PGE₂). Subsequently, rhFGF-18 reduced the expression of adhesion molecules VCAM-1 and ICAM-1, thereby decreasing THP-1 monocyte adhesion to HAVECs. Mechanistic investigations revealed that rhFGF-18 inhibits ox-LDL-induced phosphorylation and nuclear translocation of the transcriptional regulator TRIM28. Importantly, TRIM28 overexpression reversed the anti-inflammatory and anti-adhesive benefits of rhFGF-18. Collectively, this study identifies the FGF-18/TRIM28 axis as a crucial mechanism alleviating endothelial inflammation and monocyte adhesion, highlighting its potential as a therapeutic target for atherosclerosis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 5","pages":"138-146"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Gastric Cancer Biomarker in Gastric Juice: Adenosine and Its Role in the Immune Evasion Mechanism of Gastric Cancer.","authors":"Yunhai Wei, Huancen Guo, Wenjing Hu, Yishi Xiao, Jinyu Zhang, Jingrui Cao, Chu Shen, Zhongxin Wu, Lei Yin, Yuhai Gao","doi":"10.1177/10799907251415484","DOIUrl":"https://doi.org/10.1177/10799907251415484","url":null,"abstract":"<p><p>Adenosine, a common cellular metabolite, can remodel the tumor immune microenvironment. Although gastric juice is considered a potential biomarker for gastric cancer (GC), sufficient verification is still lacking. This study aims to explore the potential of gastric juice-derived adenosine as a cancer biomarker. Adenosine levels in gastric juice, blood, and tissues from patients with GC and normal controls were quantified using non-targeted metabolomics and assay kits. Structure-explorative-interactive-SAR algorithm was used to analyze and predict the binding between adenosine and adenosine A1 receptor (ADORA1). Tumor immune estimation resource algorithm was employed to examine the correlation between ADORA1 and M2 macrophage infiltration and interleukin-6 (IL-6) levels. The binding affinity between adenosine and ADORA1 was validated using the cellular thermal shift assay. The messenger RNA and protein expression levels of ADORA1, CD86, and CD206 were examined via reverse transcription-quantitative polymerase chain reaction and Western blot. The protein expression of ADORA1 in tissue samples was assessed by immunohistochemistry. Flow cytometry was employed to measure the expression of surface markers on macrophages. Levels of cytokines and IL-6 were determined using an enzyme-linked immunosorbent assay. The chemotaxis of M2 macrophages was evaluated through Transwell. <i>In vivo</i> validation was conducted using a primary GC mouse model. Adenosine was highly expressed in gastric juice and tissues of patients with GC, while no significant difference was observed in the blood. Adenosine showed a strong binding affinity for ADORA1, and its expression level was positively correlated with adenosine concentration. Moreover, ADORA1 expression in GC cells was significantly and positively associated with M2 macrophage polarization and IL-6 secretion. However, the polarization of M1 macrophages and migration of M2 macrophages remained largely unchanged during this process. Our study innovatively reveals that gastric juice adenosine holds promise as a biomarker for GC diagnosis and the cancer immune landscape.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 4","pages":"89-101"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Inflammasome-Related Genes and Their Role in Predicting Community-Acquired Pneumonia.","authors":"Jia Zhao, Li Liu, Chaoli Zhou, Dannv Yang, Jian Zhang, Qiaoping Chen","doi":"10.1177/10799907261420628","DOIUrl":"https://doi.org/10.1177/10799907261420628","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) is a common respiratory infectious disease worldwide, posing a significant threat to human health. In recent years, the crucial role of inflammasomes in the occurrence and development of pneumonia has gradually been recognized. This study aims to systematically explore potential diagnostic biomarkers related to inflammasomes in CAP. CAP transcriptome datasets GSE103119 and GSE196399 were obtained from the GEO database. First, we conducted differential expression analysis and combined it with weighted gene co-expression network analysis to screen inflammasome-related differentially expressed genes (DEIRGs). Subsequently, we carried out Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis. Then, based on multiple machine learning algorithms [least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE), Boruta, and random forest], we performed feature gene selection and combined a support vector machine (SVM) to construct a classification model. The diagnostic performance was evaluated in the training set and validation set through the receiver operating characteristic curve and precision-recall curve. Finally, we collected peripheral blood samples from 5 patients with CAP and 5 healthy controls and used quantitative real-time polymerase chain reaction (qRT-PCR) to verify the expression differences of candidate genes. A total of 414 DEIRGs were identified, mainly enriched in immune response regulation, Th17 cell differentiation, and autophagy pathways. Combined with machine learning and SVM analysis, the LASSO and RFE models showed the best performance in CAP diagnosis. Based on the intersection of these two algorithms, <i>RPL39</i>, <i>INSL3</i>, and <i>vimentin (VIM)</i> were ultimately determined as the core candidate genes. The qRT-PCR results further confirmed that in CAP peripheral blood samples, <i>INSL3</i> and <i>VIM</i> showed significantly increased expression, while <i>RPL39</i> showed decreased expression, which was consistent with the bioinformatics prediction. This study identifies <i>RPL39</i>, <i>INSL3</i>, and <i>VIM</i> as potential diagnostic markers for CAP, which may provide new evidence for early diagnosis and stratified management.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 4","pages":"102-113"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance of Biomarkers Tumor Necrosis Factor-α, Interleukin-6, and Procalcitonin in Neonatal Sepsis: A Case-Control Study.","authors":"Durgesh Kumar, Dinesh Kumar, Nishant Sharma, Pragya Saraswat, Muniba Alim, Indra Kumar Sharma, Ajai Kumar","doi":"10.1177/10799907251410722","DOIUrl":"10.1177/10799907251410722","url":null,"abstract":"<p><p>Neonatal sepsis remains a major cause of morbidity and mortality, with diagnosis complicated by nonspecific clinical signs and limited reliability of conventional laboratory tests. This study aimed to evaluate and compare the diagnostic efficacy of biomarkers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and procalcitonin (PCT) with traditional sepsis screening parameters in neonates. This hospital-based case-control study was conducted in the neonatal intensive care unit of a North Indian tertiary care medical university between September 2023 and March 2025. A total of 300 neonates were screened, of which 100 were diagnosed with sepsis (cases) and the remaining 200 served as controls. Sepsis screening, TNF-α, IL-6, PCT, and blood culture were performed to diagnose neonatal sepsis. Results of this study showed significantly higher levels of all tested biomarkers and sepsis parameters in cases compared with controls. Among biomarkers, TNF-α demonstrated the highest accuracy [area under the curve of the receiver operating characteristic (AUROC) 0.99, sensitivity 94%, specificity 100%], followed by PCT (AUROC 0.82, sensitivity 80%, specificity 82.5%) and IL-6 (AUROC 0.79, sensitivity 86%, specificity 74.5%). The study concludes that TNF-α is the most reliable biomarker for diagnosing neonatal sepsis, although a multimodal approach integrating conventional parameters with cytokines and PCT offers the best diagnostic yield. Combining early biomarkers with standard screening may improve early recognition, reduce unnecessary antibiotic exposure, and strengthen antimicrobial stewardship.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"70-75"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zika Virus Human Infection During Pregnancy Triggers a Strong and Broad Systemic Inflammatory Response.","authors":"Andréa Teixeira-Carvalho, Lis Ribeiro do Valle Antonelli, Gemilson Soares Pontes, Roberta Oliveira Prado, Bruna Stefânia Diniz Frias, Kétyllen Reis Andrade de Carvalho, Ana Carolina Campi-Azevedo, Jordana Graziela Coelho-Dos-Reis, Valdinete Alves do Nascimento, Dana Cristina da Silva Monteiro, Marineide Souza da Silva, Lígia Fernandes Abdalla, João Hugo Abdalla Santos, Matheus de Souza Gomes, Laurence Rodrigues Amaral, Patrícia Nessralla Alpoim, Lara Carvalho Godoi, Luci M S Dusse, Felipe Gomes Naveca, Olindo Assis Martins-Filho","doi":"10.1177/10799907251412083","DOIUrl":"10.1177/10799907251412083","url":null,"abstract":"<p><p>Infection by the Zika virus (ZIKV) results in a broad spectrum of disease ranging from mild to severe neurological complications. The clinical features of ZIKV human infection are similar in pregnant women compared with nonpregnant women, though symptomatic infection is more frequent during pregnancy. However, little is known about the profile of systemic immune mediators during ZIKV infection in pregnant women. To characterize immunological mediators in ZIKV infection during pregnancy, we measured the levels of circulating cytokines, chemokines, and growth factors by multiplex immunoassay in 32 pregnant women, categorized according to trimesters of pregnancy. ZIKV-infected pregnant women presented higher levels of the cytokines IL-1β, IL-6, TNF-α, IL-12, IFN-γ, IL-17, IL-1Ra, IL-4, IL-5, IL-9, and IL-10 than healthy women. Moreover, a set of pro-inflammatory biomarkers, including IL-1β, IL-6, TNF-α, IL-12, IFN-γ, CCL11, and G-CSF, showed significant increased levels in the gestational second trimester than in the first trimester, which remains elevated throughout the third trimester. In conclusion, our findings indicate that ZIKV human infection during pregnancy triggers a strong and broad systemic inflammatory response, and during the viral infection, their kinetics of the production varied according to the gestational age.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 3","pages":"59-69"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Growth Factor-beta 1 Alleviates Uterine Bleeding after Medication Abortion in Early Pregnancy by Upregulating the p53/Plasminogen Activator Inhibitor-1 Pathway.","authors":"Qianhong Huang, Haiying Lan, Hao Yu, Xianming Fei, Ying Chen","doi":"10.1177/10799907251396751","DOIUrl":"10.1177/10799907251396751","url":null,"abstract":"<p><p>TGF-β1 plays a significant role in pregnancy outcomes. This research sought to investigate whether TGF-β1 is involved in the bleeding mechanism after medication abortion (MA) in early pregnancy. The MA rat model was established <i>in vivo</i> using mifepristone and misoprostol, and trophoblasts HTR8/SVneo were treated with lipopolysaccharide <i>in vitro</i>. Changes in uterine morphology, weight, and bleeding were assessed. tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), estradiol, and progesterone levels were detected by ELISA. HE staining was employed to analyze uterine pathological changes. Apoptosis was assessed by TUNEL staining. Inflammatory cytokine expression was assessed by ELISA and qRT-PCR. Related protein levels were analyzed by Western blot. MA induction led to abnormal uterine morphology, reduced uterine weight, and heavier bleeding. MA rats showed higher tPA, uPA, IL-6, and TNF-α levels, and lower estradiol and progesterone levels compared to controls. Moreover, trophoblast tissue damage with excessive apoptosis was observed in MA rats. TGF-β1, p53, and PAI-1 levels were markedly decreased after MA induction. In HTR8/SVneo cells, lipopolysaccharide treatment significantly inhibited cellular functions, reduced TGF-β1, p53, and PAI-1 levels, and increased IL-6 and TNF-α levels. Notably, these changes were partially reversed by overexpression of <i>TGFB1</i>. In conclusion, TGF-β1 protects trophoblasts and alleviates MA-induced uterine bleeding by upregulating the p53/PAI-1 pathway.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"33-43"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Necrosis Factor: A Master Regulator in Inflammation and Disease-Pathways, Implications, and Breakthrough Therapies.","authors":"Simhadri Goud Gundrathi, Bharat Kumar Reddy Sanapalli, Ashwini Deshpande, Vidyasrilekha Sanapalli","doi":"10.1177/10799907261418982","DOIUrl":"https://doi.org/10.1177/10799907261418982","url":null,"abstract":"<p><p>Tumor necrosis factor-alpha (TNF-α), a crucial proinflammatory cytokine, is involved in immune regulation and in the pathogenesis of a variety of chronic inflammatory and autoimmune diseases. TNF-α signaling dysregulation is linked to chronic inflammatory diseases, multiorgan dysfunction, and tissue destruction through activation of TNF receptor 1 (TNFR1)-mediated inflammatory, apoptotic, and necroptotic pathways, while TNF receptor 2 (TNFR2) stimulation promotes immune regulation and tissue repair. Understanding these divergent signaling mechanisms is crucial for augmenting therapeutic interventions. The present review summarizes the molecular structure of TNF-α, compares TNFR1 and TNFR2 signaling cascades, and describes the cytokine's role in diseases such as rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, multiple sclerosis, diabetes mellitus, atherosclerosis, heart failure, systemic lupus erythematosus, and cancer. We further evaluate clinically approved TNF inhibitors and emergent investigational agents, prominent advances in receptor-selective modulation, and small-molecule TNF suppression. Overall, this review emphasizes the therapeutic potential of selectively targeting TNF-α signaling while preserving essential immunoregulatory functions, offering insights that may support next-generation drug development.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 2","pages":"44-54"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}