Journal of Interferon and Cytokine Research最新文献

{"title":"Polymorphisms in IL-10- and IL-22-Binding Protein Genes as Genetic Predictors of the Direct-Acting Antivirals Treatment Response in Patients with Chronic Hepatitis C Virus.","authors":"Komal Saleem, Hira Raheem Akbar, Zuzana Macek Jilkova, Ahmad Ali Shahid, Muhammad Idrees, Samia Afzal","doi":"10.1089/jir.2025.0005","DOIUrl":"10.1089/jir.2025.0005","url":null,"abstract":"<p><p>Cytokines are crucial in controlling inflammation during viral infection, particularly infection with the hepatitis C virus (HCV). Cytokine genetic polymorphisms can change how the immune system responds to this infection. We investigated how the HCV infection treatment was affected by single nucleotide polymorphisms in these genes. The goal of this study was to examine any connections between the cytokine gene polymorphisms for interleukins (IL)-22-binding protein rs6570136, as well as IL-10 rs1800872 and rs1878672 in the Pakistani population and responsiveness to direct-acting antivirals (DAAs) treatment. This study evaluated 155 participants, which included 55 patients who achieved sustained virologic response (SVR), 40 relapse patients, and 60 healthy controls, to assess and compare the clinical parameters. The SVR and relapse groups were compared for their allelic and genotypic frequencies. We discovered that the SVR and the relapse groups had significantly different genotype frequencies for IL-10 rs1800872 and IL-22BP rs6570136 in the Pakistani population. The G/G genotype in rs6570136 and A/A genotype in rs1800872 were significantly associated with relapse following DAA therapy, with <i>P</i> values 0.002 and 0.0004, respectively. In contrast, rs1878672 showed no significant correlation with HCV relapse, <i>P</i> = 0.63.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"196-204"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663655","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":"IFN-γ Approaches in Tumor Suppression, Its Challenges, and Future Directions: A Review of Recent Advances.","authors":"Mohammad Reza Ataherian, Nasim Hafezi, Elaheh Ferdosi-Shahandashti, Fatemeh Sarina Abdinia","doi":"10.1089/jir.2024.0259","DOIUrl":"10.1089/jir.2024.0259","url":null,"abstract":"<p><p>IFN-γ is recognized as an immunoregulatory cytokine due to its dual role in both accelerating and dampening immunological responses. Accordingly, in the context of tumor immunotherapy, the therapeutic outcome of IFN-γ is contingent upon factors such as dosage and the expression status of downstream signaling molecules. Furthermore, the coadministration of IFN-γ with various immunestimulatory agents, including anticheckpoint inhibitors, chemotherapeutic agents, and herbal-based medicines, may potentially overcome the IFN-γ-related challenges and enhance the response rate. We decipher the mechanisms of tumor cell eradication facilitated by IFN-γ, the last achievements in IFN-γ-mediated tumor immunotherapy across various cancers, and the strategies to address the failure of IFN-γ-based tumor immunotherapy. Unraveling the molecular mechanisms that lead to failure in IFN-γ-based antitumor actions could assist in pinpointing therapeutic agents that target the immune-modulatory features of IFN-γ, thereby increasing the antitumor response rate.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"164-173"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364819","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":"Correlations of Levels of Peripheral Blood Inflammatory Cytokines and Serum Lipoprotein-Associated Phospholipase-A₂ with Acute Ischemic Stroke and Their Early Prognostic Value.","authors":"Chengqing Zhong, Qin Han, Li Yang, Yidan Liu, Yun Zhang, Shucheng Li, Junmei Lv, Jianping Jiang","doi":"10.1089/jir.2024.0176","DOIUrl":"https://doi.org/10.1089/jir.2024.0176","url":null,"abstract":"<p><p>Respecting the significant role of inflammation in acute ischemic stroke (AIS) development, we explored the correlations of inflammatory cytokines and lipoprotein-associated phospholipase-A₂ (Lp-PLA₂) with AIS and their early prognostic value. The retrospectively enrolled subjects [Study (AIS patients) and Control (healthy volunteers) groups] were determined for serum index levels. Neurological impairment and early prognosis of AIS patients were assessed. The relationship of National Institutes of Health Stroke Scale (NIHSS) and the indexes and the risk factors and predictive value of peripheral blood inflammatory cytokines combined with Lp-PLA₂ for poor early prognosis were analyzed. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and Lp-PLA₂ levels rose in AIS patients, while IL-10 dropped. The NIHSS score positively correlated with IL-1β, TNF-α, and Lp-PLA₂ and negatively correlated with IL-10. As AIS aggravated, IL-1β, IL-6, TNF-α, and Lp-PLA₂ rose dependently, but IL-10 dropped. Patients in the poor early prognosis group had higher diabetes proportions, NIHSS scores and serum IL-1β, IL-6, TNF-α, and Lp-PLA₂ levels at admission, as well as lower IL-10 levels than those in the good early prognosis group. IL-6, IL-1β, TNF-α, and Lp-PLA₂ were risk factors, but IL-10 was a protective factor against poor early prognosis in AIS patients, with their combined detection showing high predictive value. Collectively, highly expressed IL-6, TNF-α, IL-1β, and Lp-PLA₂ and lowly expressed IL-10 in patients with AIS closely related to AIS development and early prognosis, and their combination could increase the predictive value of NIHSS for AIS poor early prognosis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"45 5","pages":"184-195"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011160","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":"Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated Endogenous <i>IFNLR1</i>.","authors":"Laura A Novotny, Christiana S Kappler, Eric G Meissner","doi":"10.1089/jir.2024.0262","DOIUrl":"10.1089/jir.2024.0262","url":null,"abstract":"<p><p>Distinct transcriptional isoforms of the interferon lambda receptor 1 (<i>IFNLR1</i>) are expressed in hepatocytes, but whether corresponding full-length and truncated IFNLR1 protein variants have discrete function is unclear. We quantitated <i>IFNLR1</i> isoforms in liver and blood from individuals with chronic hepatitis C virus (HCV) infection before and after antiviral treatment, hypothesizing their relative expression may differentially change during resolution of virus-induced inflammation. We also expressed FLAG-tagged IFNLR1 variants in stem cell-derived hepatocytes (iHeps) with abrogated endogenous <i>IFNLR1</i> to evaluate their function. <i>IFNLR1</i> isoforms decreased in liver and blood during treatment of HCV, but no distinct pattern of decline was observed for any individual isoform. Expression of full-length IFNLR1 enabled lambda interferon (IFNL)-induced expression of antiviral and proinflammatory genes and augmented inhibition of hepatitis B virus (HBV) replication relative to wild-type (WT) iHeps. A noncanonical IFNLR1 variant missing part of the JAK1 binding domain enabled IFNLs to induce antiviral genes but could not support induction of proinflammatory genes or augmented HBV inhibition beyond that observed in WT iHeps with intact endogenous <i>IFNLR1</i>. A secreted IFNLR1 variant had no identified function in iHeps lacking endogenous <i>IFNLR1</i>. Although relative expression of individual <i>IFNLR1</i> isoforms did not distinctly change during HCV treatment, functional studies in iHeps suggest IFNLR1 variants could function to titrate antiviral versus proinflammatory responses in hepatocytes in the context of viral hepatitis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"174-183"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391051","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":"Rosalind Franklin Society Proudly Announces the 2024 Award Recipient for <i>Journal of Interferon and Cytokine Research</i>.","authors":"Megan L Stanifer","doi":"10.1089/jir.2024.0096.rfs2024","DOIUrl":"https://doi.org/10.1089/jir.2024.0096.rfs2024","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"45 5","pages":"163"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021449","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":"Investigating Causal Associations Between Circulating Cytokines and Vestibular Disorders Using Mendelian Randomization: Insights from Large-Scale Genome-Wide Association Studies Data in European Populations.","authors":"Ke Shi, Hongwei Liu, Miaomiao Hou, Minheng Zhang","doi":"10.1089/jir.2025.0030","DOIUrl":"https://doi.org/10.1089/jir.2025.0030","url":null,"abstract":"<p><p>The presence of circulating cytokines has a significant impact on the development and progression of vestibular disorders. However, further investigation is needed to determine the direction of causation and causal effects. By applying two-sample Mendelian randomization (MR), we analyzed the potential causal connection between 41 circulating cytokines and vestibular disorders using the integrated data from genome-wide association studies (GWAS). The major analysis utilized for MR was inverse variance weighted (IVW). To examine reverse causation, we conducted reverse MR analysis. In addition, we assessed the robustness of the findings by performing pleiotropy and heterogeneity tests. Our results demonstrated that two circulating cytokines were significantly correlated with vestibular disorders risk. More specifically, vascular endothelial growth factor [IVW, odds ratio (OR) = 0.999, 95% confidence interval (CI) = 0.999-1.000, <i>P</i> = 0.046] and interleukin-7 (IVW, OR = 0.999, 95% CI = 0.998-1.000, <i>P</i> = 0.033) were negatively correlated with vestibular disorders risks, respectively. No evidence was identified to support associations between the remaining 39 circulating cytokines and vestibular disorders. These findings reveal a distinct correlation between circulating cytokines and vestibular diseases, providing a novel perspective and potential biological target for future clinical interventions for vestibular disorders.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029523","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":"Sequence Diversity in the 3' Untranslated Region of Alphavirus Modulates IFIT2-Dependent Restriction in a Cell Type-Dependent Manner.","authors":"Sarah E Hickson, Eden Brekke, Johannes Schwerk, Indraneel Saluhke, Shivam Zaver, Joshua Woodward, Ram Savan, Jennifer L Hyde","doi":"10.1089/jir.2024.0229","DOIUrl":"10.1089/jir.2024.0229","url":null,"abstract":"<p><p>Alphaviruses (family Togaviridae) are a diverse group of positive-sense RNA (+ssRNA) viruses that are transmitted by arthropods and are the causative agent of several significant human and veterinary diseases. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs) are a family of RNA-binding IFN-stimulated genes (ISGs) that are highly upregulated following viral infection and have been identified as potential restrictors of alphaviruses. The mechanism by which IFIT1 restricts RNA viruses is dependent on self and non-self-discrimination of RNA, and alphaviruses evade this recognition via their 5' untranslated region (UTR). However, the role of IFIT2 during alphavirus replication and the mechanism of viral replication inhibition is unclear. In this study, we identify IFIT2 as a restriction factor for Venezuelan equine encephalitis virus (VEEV) and show that IFIT2 binds the 3' 3'UTR of the virus. We investigated the potential role of variability in the 3'UTR of the virus affecting IFIT2 antiviral activity by studying infection with VEEV. Comparison of recombinant VEEV clones containing 3'UTR sequences derived from epizootic and enzootic isolates exhibited differential sensitivity to IFIT2 restriction <i>in vitro</i> infection studies, suggesting that the alphavirus 3'UTR sequence may function in part to evade IFIT2 restriction. <i>In vitro</i> binding assays demonstrate that IFIT2 binds to the VEEV 3'UTR; however, in contrast to previous studies, VEEV restriction did not appear to be dependent on the ability of IFIT2 to inhibit translation of viral RNA, suggesting a novel mechanism of IFIT2 restriction. Our study demonstrates that IFIT2 is a restriction factor for alphaviruses and variability in the 3'UTR of VEEV can modulate viral restriction by IFIT2. Ongoing studies are exploring the biological consequences of IFIT2-VEEV RNA interaction in viral pathogenesis and defining sequence and structural features of RNAs that regulate IFIT2 recognition.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"133-149"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615687","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":"Research Hotspots of Interferon Gamma in the Treatment of Lung Cancer: A Bibliometric Analysis Based on CiteSpace.","authors":"Zhen Lv, Jianjun Wu","doi":"10.1089/jir.2024.0242","DOIUrl":"10.1089/jir.2024.0242","url":null,"abstract":"<p><p>Interferon-gamma (IFN-γ) is an important cytokine associated with antitumor immunity and has been implicated in the pathogenesis and progression of lung cancer. Nevertheless, no bibliometric analyses have been published in this field to date, and thus we aim to address this gap in knowledge. A search of the Web of Science (WOS) for literature related to the treatment of lung cancer with IFN-γ was conducted from 2002 to 2024. The extracted information from the included articles was subjected to visual analysis, and network diagrams were generated using software such as CiteSpace and VOSviewer. In total, 589 articles related to the treatment of lung cancer with IFN-γ were included in WOS between 2002 and 2024. The number of articles and citation frequency generally showed an increasing trend year by year. The United States and the University of California are the countries and institutions with the largest number of articles. The researcher who made the largest contribution to this field was Xin Cai from China (6). The <i>Journal for ImmunoTherapy of Cancer</i> published the largest number of relevant papers in the field (16 papers, IF = 12.469). The research hotspots in the field of immune escape in recent years have been IFN-γ, mechanism, immune checkpoints, and microtumor inhibitors. The field of IFN-γ treatment of lung cancer is evolving at a rapid pace. The current research focus within this field is on elucidating the mechanism of IFN-γ treatment of lung cancer, investigating the role of immune checkpoint inhibitors, and examining the tumor microenvironment and other pertinent topics.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"109-118"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059375","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":"Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells.","authors":"Brittany S Ulloa, Isaac Barber-Axthelm, Bryan Berube, Malcolm Duthie, Steve Reed, Ram Savan, Michael Gale","doi":"10.1089/jir.2024.0195","DOIUrl":"10.1089/jir.2024.0195","url":null,"abstract":"<p><p>Retinoic acid-inducible gene I (RIG-I) is a critical sensor of viral RNA and is activated in response to binding to RNA containing exposed 5'-triphosphate (5'ppp) and poly-uridine to trigger innate immune activation and response including induction of type I and III interferons (IFNs). RIG-I signaling plays a key role in not only restricting RNA virus infection but also suppressing tumor progression via oncolytic signaling. We evaluated the actions of a specific RIG-I agonist RNA (RAR) as a potential therapeutic against model tumor cell lines representing hepatocellular carcinoma (HCC). RAR constitutes a synthetic-modified RNA motif derived from the hepatitis C virus genome that is specifically recognized by RIG-I and induces innate immune activation when delivered to cells. We found that RAR directs RIG-I-dependent signaling to drive HCC cell death. Analysis of knockout cell lines lacking RIG-I, mitochondrial activator of virus signaling, or IRF3 confirmed that RAR-induced cell death signaling propagates through the RIG-I-like receptor (RLR) pathway to mediate caspase activation and HCC cell death. RAR-induced cell death is potentiated by type I IFN. Thus, RAR actions trigger HCC cell death through RIG-I linkage of RLR, caspase, and IFN signaling programs. RAR offers a potent application in antitumor therapeutic strategies leveraging innate immunity against liver cancer.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"119-132"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of miR-155 Attenuates Lung Cytokine Storm Induced by SARS-CoV-2 Infection.","authors":"Dharmendra Kumar Soni, Juan Cabrera-Luque, Swagata Kar, Anwar Ahmed, Chaitali Sen, Joseph Devaney, Roopa Biswas","doi":"10.1089/jir.2024.0253","DOIUrl":"10.1089/jir.2024.0253","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is a deadly human viral disease with a high rate of infection, morbidity, and mortality. Although vaccines and antiviral treatments are available, hospitalizations remain steady, and concerns about long-term consequences persist. Therefore, there is a great urgency to develop novel therapies. Here, we analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Endogenous microRNAs (miRNAs, miRs) are key molecules in preventing viral entry and replication while building an antiviral cellular defense. Our study reveals that miR-155 expression is elevated in patients with COVID-19. Using a mouse model transgenic for human angiotensin-converting enzyme receptor 2, we evaluated the potential of anti-miR-155 therapy. Treating SARS-CoV-2-infected mice with anti-miR-155 significantly reduced miR-155 expression, improved survival, and slightly increased body weight. Notably, these mice showed altered expression of cytokines in the lungs. These findings suggest anti-miR-155 could be a promising therapy to mitigate the cytokine storm and long-lasting symptoms induced by SARS-CoV-2 infection, improving public health outcomes and enhancing global pandemic preparedness.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"150-161"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414570","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}