Journal of Interferon and Cytokine Research最新文献

{"title":"Low Gut <i>Bifidobacterium</i> Relative Abundance and Low Intake of Zinc, Omega-3 Fatty Acids, and Vitamin D Are Associated With Inflammation in Children.","authors":"Cinthia Denisse Pérez-Carrillo, Juan Carlos Ayala-García, Cinthya Estefhany Díaz-Benítez, Alfredo Lagunas-Martínez, Margarita Bahena-Román, Lilia Juárez-Palma, Miguel Cruz, Ana Isabel Burguete-García","doi":"10.1177/10799907261470545","DOIUrl":"10.1177/10799907261470545","url":null,"abstract":"<p><p>Maintaining optimal health in childhood is essential for proper physical, motor, and neurological development. A balanced gut microbiota and adequate micronutrient intake support immune regulation, preservation of the intestinal barrier, and reduction of chronic inflammation. In contrast, unhealthy diets are linked to lower nutrient intake and disruptions in gut microbial composition. In this cross-sectional study of 209 children aged 6-12 years in Mexico City, we evaluated the interaction between the relative abundance of <i>B. longum</i>, <i>B. adolescentis</i>, and <i>B. breve</i> and the intake of zinc, omega-3 fatty acids, and vitamin D, and their association with serum cytokines (IL-6, IL-10, tumor necrosis factor-alpha, and adiponectin) using logistic regression models. We observed that children with low <i>B. adolescentis</i> abundance and low zinc intake had higher odds of elevated IL-6 levels. Similarly, low <i>B. adolescentis</i> abundance combined with low vitamin D intake was associated with increased odds of elevated IL-6. Low <i>B. breve</i> abundance with low zinc intake also showed higher odds of elevated IL-6. Conversely, low <i>B. longum</i> abundance with low vitamin D and omega-3 intake was associated with higher odds of elevated IL-10 levels. These findings suggest that reduced <i>Bifidobacterium</i> abundance, combined with low micronutrient intake, is associated with altered cytokine profiles, contributing to immune dysregulation and inflammation in children.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"352-361"},"PeriodicalIF":1.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604222","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":"Targeting MDA5-Mediated Interferon Responses in Type 1 Diabetes: Structural Insights, Mechanism, and Potential Therapeutic Approaches.","authors":"Opeoluwa F Iwaloye, Clayton E Mathews, Danmeng Li","doi":"10.1177/10799907261467555","DOIUrl":"10.1177/10799907261467555","url":null,"abstract":"<p><p>Melanoma differentiation-associated protein 5 (MDA5), encoded by <i>IFIH1</i>, is a cytosolic double-stranded RNA (dsRNA) sensor. Mutation of <i>IFIH1</i> resulting in MDA5 deficiency causes immune dysfunction and predisposition to specific respiratory viral pathogens due to the inability of innate immune system to detect viral dsRNA. Additionally, gene variants in <i>IFIH1</i> have been linked to autoimmunity, including type 1 diabetes. To understand structure-function, we integrate structural biology and signaling principles to explain how MDA5 architecture governs interactions with dsRNA and type 1 interferon (T1-IFN) outputs. MDA5 binds dsRNA via its helicase core and C-terminal domain, uses ATP-dependent conformational cycling to assemble filaments, and exposes N-terminal CARDs that nucleate mitochondrial antiviral signaling protein polymerization, activating TBK1/IKKε-IRF and NF-κB programs that amplify T1-IFN production and inflammatory gene expression. Risk-associated <i>IFIH1</i> alleles are predicted to increase T1-IFN production/activation thresholds, whereas rare loss-of-function variants attenuate T1-IFN outputs and confer protection. Finally, we outline therapeutic entry points that preserve antiviral defense while constraining chronic T1-IFN signaling to restrain MHC class I expression, chemokine production, and autoreactive T-cell recruitment. Targeting downstream pathways with small molecule inhibitors may delay early autoimmunity and target tissue functions in genetically defined subgroups.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"325-338"},"PeriodicalIF":1.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447721","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":"Translational Analysis of Cytokine SNPs Reveals an Interplay Between Immune Response and Glucose Metabolism Following Mild-to-Moderate COVID-19.","authors":"Nipaporn Teerawattanapong, Ganyalak Chaimaha, Tassanee Narkdontri, Suavaluk Songlilitchuwong, Saranya Innang, Sarocha Suthon, Watip Tangjittipokin","doi":"10.1177/10799907261466763","DOIUrl":"10.1177/10799907261466763","url":null,"abstract":"<p><p>This study explores the relationship between genetic factors, immune response, and clinical characteristics in patients with post-COVID-19. A total of 190 participants with mild to moderate symptoms were recruited from Siriraj Hospital. Cytokine single-nucleotide polymorphisms (SNPs) (<i>IL1β</i>: rs1143643; <i>IL4</i>: rs2243250, rs2243290; <i>IFNγ</i>: rs2069727, rs2430561; <i>IL17A</i>: rs2275913, rs3819025; <i>TGFβ1</i>: rs1800469) were genotyped using rhAmp™ SNP Genotyping. Participants were stratified by neutralizing antibody (Nab) and anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) levels. Patients with high Nab levels had significantly higher HbA1c compared with those with low Nab levels (5.98 ± 1.21% vs. 5.66 ± 0.79%, <i>P</i> = 0.03). The TC genotype of <i>TGFβ1</i> rs1800469 was associated with a lower frequency of patients in both the high Nab group (TT vs. TC: odds ratio [OR] = 0.445, <i>P</i> = 0.019) and in the high anti-RBD IgG group (TT vs. TC: OR = 0.472, <i>P</i> = 0.032). Similarly, the TA genotype of <i>IFNγ</i> rs2430561 was associated with a reduced frequency of patients in the high anti-RBD IgG group (TT vs. TA: OR = 0.245, <i>P</i> = 0.025). One month postinfection, Nab and low-density lipoprotein levels were reduced in patients with TC of rs1800469 (<i>P</i> = 0.028 and <i>P</i> = 0.018, respectively). A moderate positive correlation was observed between baseline Nab levels and HbA1c at 3 months in patients with the AA genotype of rs2430561 (<i>r</i> = 0.213, <i>P</i> = 0.035). These findings may suggest a possible link between genetic variants, glucose levels, and antibody responses in patients with post-COVID-19, providing insights into long-term management strategies.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"339-351"},"PeriodicalIF":1.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376015","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":"IL-37a, an Anti-Inflammatory Molecule and a Nuclear Cytokine: Linking Alternative Splicing, Nuclear Trafficking, and Epigenetic Regulation of Inflammation.","authors":"Zhi-Ya Wang, Yong-Qi Feng, Xin-Xin Hu, Yan-Yu Zhang, Xiao-Yun Zhang, Sen Wang, Jian-Jun Xie","doi":"10.1177/10799907261499951","DOIUrl":"https://doi.org/10.1177/10799907261499951","url":null,"abstract":"<p><p>Interleukin-37 (IL-37) is an anti-inflammatory member of interleukin-1 family. Alternative splicing generates five isoforms (IL-37a-e) with distinct exon compositions. IL-37a has recently attracted increasing attention because it uniquely retains exon 3. Exon 3 encodes an N-terminal nuclear localization sequence (NLS) that enables autonomous nuclear translocation and harbors an elastase cleavage site at L21/R22. Elastase cleavage produces N-terminal IL-37a (NIL-37a) and mature IL-37a (mIL-37a). Full-length IL-37a and NIL-37a can exert IL-1R8-independent nuclear regulatory and anti-inflammatory effects in the endotoxemic shock model. Nuclear IL-37a recruits a WDR5/MLL4/C/EBPβ-associated complex to promote <i>PPARG</i> transcription, thereby linking cytokine signaling with chromatin regulation and PPARγ-mediated inflammatory control. These findings highlight IL-37a as a mechanistically distinct isoform and illustrate how isoform-specific sequence composition, proteolytic processing, and subcellular localization can diversify cytokine functions. This review synthesizes available evidence regarding the molecular basis of IL-37a nuclear activity, compartmentalized signaling and receptor-independent epigenetic regulation, in the context of nuclear cytokine biology and immunometabolic control. Collectively, IL-37a is a mechanistically distinct isoform whose alternative splicing, proteolytic processing, and nuclear trafficking shape compartment-specific signaling. In LPS-induced endotoxic shock, nuclear IL-37a acts independently of IL-1R8 to upregulate PPARγ through WDR5/MLL4/C/EBPβ-associated chromatin regulation; however, isoform-specific evidence requires further validation, particularly in humans.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"10799907261499951"},"PeriodicalIF":1.9,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224375","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":"A Distinct c-Raf-MEK1/2-p38 MAPK-Caspase Signaling Pathway Mediates TNF-α-Induced Rapid and Non-Lytic Neutrophil Extracellular Trap Formation in Human Neutrophil-Like Cells.","authors":"Sung-Hun Woo, Yerang Lee, Sung Hoon Kim, Byung Chul Jung, Yoon Suk Kim","doi":"10.1177/10799907261473767","DOIUrl":"10.1177/10799907261473767","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) contribute to host defense by trapping pathogens. However, excessive or dysregulated NET formation is implicated in the pathogenesis of various conditions, including thrombosis, autoimmune diseases, and cancer. Despite their clinical significance, the specific intracellular signaling pathways underlying NET formation in response to proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), remain incompletely defined. Thus, in the present study, we aimed to elucidate the mechanisms underlying TNF-α-induced NET formation in human neutrophil-like differentiated HL-60 (dHL-60) cells. TNF-α induced rapid, non-lytic NET formation in dHL-60 cells without compromising cell viability. Mechanistically, TNF-α activated a signaling cascade involving c-Raf, MEK1/2, and p38 mitogen-activated protein kinase (MAPK). This signaling cascade regulated the sequential caspase activation, with caspase-2 acting upstream of caspase-1 cleavage to promote NET formation. Collectively, these findings suggest that TNF-α induces non-lytic NET formation via a defined c-Raf-MEK1/2-p38 MAPK-caspase pathway and a distinct caspase hierarchy. This mechanism offers a valuable experimental model for studying NET-mediated pathologies in proinflammatory environments.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"305-317"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684681","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":"Vaspin-Cytokine Interactions in Chronic Low Back Pain: Links Between Obesity, Inflammation, and Traction Therapy Response.","authors":"Marzena Ratajczak, Alexander Kalinkovich, Gregory Livshits","doi":"10.1177/10799907261465506","DOIUrl":"10.1177/10799907261465506","url":null,"abstract":"<p><p>Interest in identifying biomarkers that reflect spine condition and support therapy monitoring has grown. Since low-grade inflammation and comorbidities can complicate treatment, they should be considered in research. Vaspin (SERPINA12) has been linked to low back pain (LBP) severity and disability, highlighting its potential as a biomarker connecting LBP and adipose tissue inflammation. The study aimed to assess the effect of traction therapy on serum vaspin levels and compare responses between women with obesity and normal BMI. A secondary aim was to explore associations between vaspin, LBP severity, disability scores, and selected inflammatory markers. It is a prospective clinical trial. Women aged 34-50 years with chronic LBP were divided into two groups: those with normal BMI and those with obesity. Both groups underwent 20 30-min sessions of lumbar traction therapy. At baseline and after therapy, LBP intensity, the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RMDQ) were assessed, and blood samples were collected for analysis of vaspin, RANTES, interleukin (IL)-2, IL-17A, IL-4, and IL-10. After completing the traction therapy, there was a significant decrease in LBP, ODI, and RMDQ and an increase in the circulating levels of IL-10, regardless of BMI. However, vaspin concentration increased significantly only in women with normal BMI. Post-therapy, vaspin negatively correlated with ODI. IL-4 and IL-17A levels also correlated with vaspin, positively in women with normal BMI and negatively in those with obesity. Obesity-related inflammation may alter the biochemical response to traction therapy. Increases in vaspin concentration were found exclusively in women with normal BMI, indicating a possible BMI-dependent association between circulating vaspin concentrations and response to therapy.Registration: The study was registered at ClinicalTrials.gov with the ID number NCT04507074.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"294-304"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345589","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":"Targeted Inhibition of <i>RPA3</i> Impairs Breast Cancer Progression Through Suppressing TGF-β Signaling Pathway-Mediated Autophagy.","authors":"Zhiyi Zhang, Haipeng Yu, Liqun Hao","doi":"10.1177/10799907261465503","DOIUrl":"10.1177/10799907261465503","url":null,"abstract":"<p><p>As a key component of the replication protein A (RPA) complex, <i>RPA3</i> has been identified as oncogenic in multiple solid tumors. However, its specific role in breast cancer remains poorly understood. <i>RPA3</i> expression and its prognostic relevance in breast cancer were assessed based on the public databases. To further confirm the biological function of <i>RPA3</i>, we knocked down <i>RPA3</i> in the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7) and then conducted Cell Counting Kit-8, colony formation, Western blot, immunofluorescence, and transmission electron microscopy. <i>In vivo</i> effects of <i>RPA3</i> were tested in a xenograft model. We found that high expression of <i>RPA3</i> in breast cancer predicted adverse patient outcomes. <i>RPA3</i> was mainly involved in multiple oncogenic signaling pathways, including the transforming growth factor-β (TGF-β) pathway. <i>RPA3</i> knockdown effectively suppressed cancer cell proliferation <i>in vitro</i> and <i>in vivo</i>. Mechanistically, <i>RPA3</i> knockdown decreased TGF-β1 promoter activity and reduced TGF-β1 expression at mRNA and protein levels, accompanied by decreased p-Smad2/3 levels. <i>RPA3</i> knockdown also significantly blocked autophagy, as evidenced by decreased microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, increased sequestosome 1 (p62) level, and reduced LC3 puncta. Notably, pharmacological activation of the TGF-β pathway partially reversed autophagy alterations induced by <i>RPA3</i> knockdown. These data support the possibility of <i>RPA3</i> as a therapeutic target for breast cancer.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"285-293"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391114","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":"Stromal Expression of TNF-α and Its Receptors TNFR1 and TNFR2: Association with Blood Count Parameters in Ovarian Cancer.","authors":"Rosekeila Simões Nomelini, Marcela Moisés Maluf Sanguinete, Clícia Chagas Modesto, Fabrícia Fernanda Barros Cruz, Neila Caroline Alves Amaral, Millena Prata Jammal, Eliângela de Castro Côbo, Renata Margarida Etchebehere, Eddie Fernando Candido Murta","doi":"10.1177/10799907261487838","DOIUrl":"https://doi.org/10.1177/10799907261487838","url":null,"abstract":"<p><p>The objective of this study was to evaluate the association between immunostaining of tumor necrosis factor-alpha (TNF-α) and its receptors in the stroma of malignant ovarian neoplasm with hemogram parameters and tumor markers. Women with a confirmed diagnosis of malignant or borderline ovarian neoplasm were included (<i>n</i> = 43). Age, hormonal status, histological type, histological grade, staging, type of carcinogenesis, and blood count parameters were recorded. For the immunohistochemical study, TNF-α and its receptors were evaluated in peritumoral stroma. Receiver operating characteristic curve and multivariate analysis were performed. The level of significance was <0.05. For TNF-α, there was statistical significance for basophils (cutoff value >0) and neutrophils (cutoff value ≤3,900) between strong and weak immunostaining. In relation to TNF-α receptor 1 (TNFR1), a cutoff value of monocytes >312 per mm³ was found. Regarding TNF-α receptor 2 (TNFR2), the cutoff value of CA-125 was ≤95.16 U/mL. Still regarding TNFR2, the cutoff value for the absolute platelet count was ≤298,000 per mm³. Multivariate analysis showed that an absolute monocyte count >312 per mm³ is associated with strong stromal immunostaining of TNFR1, and a platelet count ≤298,000 per mm³ is associated with strong stromal immunostaining of TNFR2. Therefore, an absolute monocyte count >312 per mm³ is associated with strong stromal immunostaining of TNFR1, and a platelet count ≤298,000 per mm³ is associated with strong stromal immunostaining of TNFR2.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"10799907261487838"},"PeriodicalIF":1.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969387","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":"Suppression of Lipopolysaccharide-Induced Cytokine Production by Chemokine Ligand-1 Short Hairpin RNA.","authors":"Thuraya Elgreu, Serge Dibart, Xiaoren Tang","doi":"10.1177/10799907261445142","DOIUrl":"https://doi.org/10.1177/10799907261445142","url":null,"abstract":"<p><p><i>Objectives:</i> Lipopolysaccharide (LPS) from oral Gram-negative bacteria induces inflammatory responses involving the chemokine CXCL1. Although CXCL1 is known to mediate inflammation, its role in disease processes remains incompletely understood. This study aimed to investigate the biological function of CXCL1, evaluate shRNAs as inhibitors, and determine whether CXCL1 suppression is associated with reduced LPS-induced cytokine production.<i>Materials and Methods:</i> Human CXCL1 cDNA was cloned into recombinant plasmid DNA and transfected into THP-1 monocyte-like cells. CXCL1-regulated cytokines, including tumor necrosis factor alpha (TNF-α) and IL-1β, were quantified by enzyme-linked immunosorbent assay (ELISA) following treatment with pharmacologic and molecular inhibitors. Multiple CXCL1-targeting shRNAs were designed, synthesized, and tested. The specificity of CXCL1 shRNA-mediated inhibition of LPS-induced proteins was analyzed using ELISA and a hybrid method analysis.<i>Results:</i> Treatment with a Janus kinase inhibitor or CXCL1 shRNA#2 significantly suppressed CXCL1 expression, resulting in reduced production of TNF-α and other pro-inflammatory cytokines, suggesting a regulatory role for CXCL1. CXCL1 shRNA#2 also markedly inhibited LPS-induced chemokines, kinases, transcription factors, and apoptotic genes, demonstrating broad anti-inflammatory effects.<i>Conclusions:</i> CXCL1 appears to play a regulatory role in LPS-dependent inflammatory pathways, and its suppression by shRNA or pharmacologic inhibitors effectively reduces cytokine production. These findings provide insight into CXCL1-associated mechanisms while highlighting the need for further mechanistic studies to elucidate the precise signaling pathways involved and may inform the development of potential therapeutic strategies for inflammatory diseases.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"46 9","pages":"272-277"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664035","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 Serum 25-Hydroxyvitamin D Response to Supplemental Vitamin D Is Temporarily Blunted with Elevated Circulating Cytokines at Baseline.","authors":"Tyler Barker, Victoria E Rogers, Vanessa T Henriksen","doi":"10.1177/10799907261465487","DOIUrl":"10.1177/10799907261465487","url":null,"abstract":"<p><p>This investigation examined whether initially elevated serum cytokine concentrations associate with a lower serum 25-hydroxyvitamin D (25(OH)D) increase shortly after initiating supplemental vitamin D. This secondary analysis combined data from separate randomized, double-blind, placebo-controlled studies consisting of reportedly healthy adults and individuals with knee osteoarthritis who received supplemental vitamin D. Subjects were separated into 2 groups based on serum IL-6 concentrations at baseline (Bsl; prior to supplemental vitamin D): (1) non-elevated IL-6 (<2.5 pg/mL; <i>n</i> = 22) or (2) elevated IL-6 (≥2.5 pg/mL; <i>n</i> = 11). Reportedly healthy adults and knee osteoarthritis subjects with elevated IL-6 were matched (1:2) to those with non-elevated IL-6. Matching was based on condition (healthy adults and knee osteoarthritis), age (±3.0 <i>y</i>), sex, body mass index (±3.0 kg/m²), and dose of supplemental vitamin D (cholecalciferol, 4,000 or 8,000 IU/d). Serum cytokine concentrations at Bsl and serum 25(OH)D concentrations at Bsl and following 7 and 28-d of daily vitamin D supplementation are reported here. Serum IL-6 and other cytokines (GM-CSF, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-8, and TNF-α) were significantly increased in the elevated compared to the non-elevated IL-6 group at Bsl (all <i>P</i> < 0.05). Serum 25(OH)D concentrations at Bsl, 7-d, and 28-d were not significantly different between IL-6 groups. The increase in serum 25(OH)D from Bsl to 7-d (7-dΔ) was significantly lower in the elevated compared to the non-elevated IL-6 group (<i>P</i> < 0.05). The 7-dΔ in serum 25(OH)D displayed modest inverse associations with Bsl serum 25(OH)D (β = -0.46, <i>P</i> < 0.01) and IL-6 (β = -0.43, <i>P</i> < 0.01). However, the 28-dΔ in serum 25(OH)D was inversely associated with Bsl serum 25(OH)D (β = -0.57, <i>P</i> = 0.01) but not with Bsl serum IL-6 (β = 0.10, <i>P</i> = 0.31). We conclude that the serum 25(OH)D response to supplemental vitamin D is temporarily blunted with elevated baseline circulating IL-6 and other cytokines, but this response diminished as supplementation continued.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"264-271"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345557","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}