{"title":"The Interplay Between Cytokines and MicroRNAs to Regulate Metabolic Disorders.","authors":"Li Zhang, Li Zhang, Huan Chen, Xiangyong Xu","doi":"10.1089/jir.2024.0059","DOIUrl":"10.1089/jir.2024.0059","url":null,"abstract":"<p><p>Metabolic disorders represent significant public health challenges worldwide. Emerging evidence suggests that cytokines and microRNAs (miRNAs) play crucial roles in the pathogenesis of metabolic disorders by regulating various metabolic processes, including insulin sensitivity, lipid metabolism, and inflammation. This review provides a comprehensive overview of the intricate interplay between cytokines and miRNAs in the context of metabolic disorders, including obesity, type 2 diabetes, and cardiovascular diseases. We discuss how dysregulation of cytokine-miRNA networks contributes to the development and progression of metabolic disorders and explore the therapeutic potential of targeting these interactions for disease management.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"337-348"},"PeriodicalIF":1.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855731","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}
Nikola Ralchev, Silviya Lyubenova Bradyanova, Yana Valerieva Doneva, Nikolina Mihaylova, Elena Vikentieva Elefterova-Florova, Andrey Ivanov Tchorbanov, José Francisco Muñoz-Valle, Maria Cristina Petralia, Ferdinando Nicoletti, Paolo Fagone
{"title":"Cytokine Signatures and Immune Dysregulation in COVID-19 Patients: Transcriptomic and Serum Analysis.","authors":"Nikola Ralchev, Silviya Lyubenova Bradyanova, Yana Valerieva Doneva, Nikolina Mihaylova, Elena Vikentieva Elefterova-Florova, Andrey Ivanov Tchorbanov, José Francisco Muñoz-Valle, Maria Cristina Petralia, Ferdinando Nicoletti, Paolo Fagone","doi":"10.1089/jir.2024.0083","DOIUrl":"10.1089/jir.2024.0083","url":null,"abstract":"<p><p>COVID-19, caused by the SARS-CoV-2 virus, has caused a global health crisis, necessitating a deeper understanding of its pathophysiology. In this study, we explored the immune and hematological dynamics in COVID-19 patients to gain insights into disease severity and prognosis. Our findings revealed distinct cytokine profiles in moderate and severe cases. <i>IL12A</i> was significantly upregulated in peripheral blood mononuclear cells from moderate cases, suggesting a potential role in initiating an effective immune response. Conversely, severe cases exhibited downregulation of key pro-inflammatory cytokines (<i>IL23A, TNFalpha, IL1B, and IFNG</i>) alongside an upregulation of the immunosuppressive <i>IL10</i>, indicative of a dysregulated immune environment. Serum analysis showed elevated IL6 and IL10 levels in both moderate and severe cases, emphasizing their potential as markers for disease severity. Notably, no significant differences in serum cytokines were found between recovery and lethal cases. In lethal cases of COVID-19, elevated D-dimer, urea, and creatinine correlated with IL6 and IL10. This study contributes valuable information to the ongoing efforts to understand and manage the dysregulated immune responses underlying COVID-19 pathology.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"379-385"},"PeriodicalIF":1.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476789","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}
Anthony T Reder, Aika Goel, Tzintzuni Garcia, Xuan Feng
{"title":"Alternative Splicing of RNA Is Excessive in Multiple Sclerosis and Not Linked to Gene Expression Levels: Dysregulation Is Corrected by IFN-β.","authors":"Anthony T Reder, Aika Goel, Tzintzuni Garcia, Xuan Feng","doi":"10.1089/jir.2024.0032","DOIUrl":"10.1089/jir.2024.0032","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"355-371"},"PeriodicalIF":1.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855401","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":"The Role of Interleukin-22 in Controlling Virus Infections at Mucosal Surfaces.","authors":"Cuncai Guo, Steeve Boulant, Megan Lynn Stanifer","doi":"10.1089/jir.2024.0097","DOIUrl":"10.1089/jir.2024.0097","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"349-354"},"PeriodicalIF":1.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310912","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":"The Effective Inhibitory Concentration of Interferon-β Correlates with Infectivity and Replication Fitness of SARS-CoV-2 Variants.","authors":"Janmejay Singh, Anbalagan Anantharaj, Parveen Kumar, Rajesh Pandey, Anil Kumar Pandey, Guruprasad R Medigeshi","doi":"10.1089/jir.2024.0016","DOIUrl":"10.1089/jir.2024.0016","url":null,"abstract":"<p><p>India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-β (IFN-β) treatment and found that XBB.1.16 variant was most sensitive to IFN-β. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"325-333"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335914","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":"Activated and Naïve Allogenic Human Placental Mesenchymal Stromal Cells Exert an Immunomodulatory Effect on Hidradenitis Suppurativa Patient Peripheral Blood Mononuclear Cells.","authors":"Vaiva Jariene, Paulius Valiukevicius, Justinas Maciulaitis, Ugne Kuzaityte, Ruta Insodaite, Ieva Ciapiene, Romaldas Maciulaitis, Skaidra Valiukeviciene","doi":"10.1089/jir.2024.0035","DOIUrl":"10.1089/jir.2024.0035","url":null,"abstract":"<p><p>This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and <i>IL-17A</i> gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (<i>P</i> = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (<i>P</i> = 0.022) and IL-17A (<i>P</i> = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the <i>IL-1β, IL-36α</i>, and <i>TNF-α</i> genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"291-299"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859412","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":"Evaluation of Serum/Plasma Levels of Interleukins (IL-6, IL-12, IL-17, IL-18, and IL-23) in Adults and Children with Obstructive Sleep Apnea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.","authors":"Amin Golshah, Masoud Sadeghi, Edris Sadeghi","doi":"10.1089/jir.2024.0057","DOIUrl":"10.1089/jir.2024.0057","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (<i>P</i> value < 0.00001), for IL-17 level were 0.74 (<i>P</i> value = 0.14), and for IL-18 level were 0.43 (<i>P</i> value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (<i>P</i> value < 0.00001), for IL-12 was 0.47 (<i>P</i> value = 0.10), for IL-17 was 2.21 (a <i>P</i> value = 0.24), for IL-18 was 0.19 (<i>P</i> value = 0.07), and for IL-23 was 2.46 (<i>P</i> value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"300-315"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957876","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}
Mojtaba Shohan, Mohammad Reza Mahmoudian-Sani, Ali Saeedi-Boroujeni, Sara Iranparast, Roohangiz Nashibi, Farhad Abolnezhadian, Farid Yousefi, Seyed Mohammad Alavi, Bahman Cheraghian, Ali Khodadadi
{"title":"The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19.","authors":"Mojtaba Shohan, Mohammad Reza Mahmoudian-Sani, Ali Saeedi-Boroujeni, Sara Iranparast, Roohangiz Nashibi, Farhad Abolnezhadian, Farid Yousefi, Seyed Mohammad Alavi, Bahman Cheraghian, Ali Khodadadi","doi":"10.1089/jir.2024.0018","DOIUrl":"10.1089/jir.2024.0018","url":null,"abstract":"<p><p>As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"316-324"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911849","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":"Interferon-Alpha Induces Psoriatic Inflammation in Mice by Phosphorylating FOXO3.","authors":"Hanjiang Gu, Xiaoyu Wang, Mei Lu, Yaqi Wang, Kaixuan Ren, Yitian Zhang, Wei Liu, Guanglei Hu, Weihui Zeng, Yumin Xia","doi":"10.1089/jir.2023.0225","DOIUrl":"10.1089/jir.2023.0225","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"260-270"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335913","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":"Cell-Mediated Immune Response Against <i>Mycobacterium tuberculosis</i> and Its Potential Therapeutic Impact.","authors":"Harshika Khanna, Sarika Gupta, Yasmeen Sheikh","doi":"10.1089/jir.2024.0030","DOIUrl":"10.1089/jir.2024.0030","url":null,"abstract":"<p><p>Cell-mediated immune response is critical for <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with <i>M.tb</i>. A complex array of cytokines and chemokines are involved in the immune response against <i>M.tb</i>; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in <i>M.tb</i> infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"244-259"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859384","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}