Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 441 450 Soheila Alyasin Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Zahra Kanannejad Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Hesamodin Nabavizadeh Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Hossein Esmaeilzadeh Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Erfan Sadeghi Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Hafez Shojaadini Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran Ashkan Akbarzadeh Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran Nazanin Ayareh Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran Leila Johari Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2024 11 17 2025 01 11 Fractional exhaled nitric oxide (FeNO) has emerged as a potential biomarker for differentiating between various causes of non-chronic cough, particularly in conditions associated with airway inflammation, such as asthma. This study aimed to evaluate the diagnostic efficacy of FeNO in pediatric patients with non-chronic cough and its ability to differentiate between asthma exacerbations and respiratory tract infections. Seventy-five pediatric patients aged 10-18 years with non-chronic cough were categorized into three groups: good control asthma (GCA, n=28), acute asthma exacerbation (AAE, n=26), and respiratory tract infection (RTI, n=21). Clinical assessments included FeNO measurement, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), and immunoglobulin E (IgE) levels. Univariate and multivariate multinomial logistic regression models were applied to assess the predictive value of these variables. FeNO levels were significantly higher in the AAE group (46.58±22.66 ppb) compared to the GCA and RTI groups, indicating elevated eosinophilic airway inflammation in asthma exacerbations. CRP was a significant predictor of both AAE and RTI, with a one-unit increase in CRP increasing the odds of exacerbation or infection by 2.6-fold. Body max index (BMI) was inversely associated with the risk of RTI. Hemoglobin, platelet count, and IgE levels were significantly higher in the AAE group compared to the other groups, while WBC counts, though elevated, were not statistically significant. FeNO associated with other inflammatory markers, including CRP and BMI, could enhance diagnostic accuracy and inform clinical decision-making in managing pediatric respiratory conditions. To confirm these results, future studies with larger sample sizes should be performed.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4245 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4245/2174

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 403 427 Somayeh Mami Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sajjad Shekarchian Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohammad Mousavi Department of Hematology, School of Para-Medicine, Bushehr University of Medical Sciences, Bushehr, Iran AND Clinical Research Development Center, The Persian Gulf Martyrs Hospital, Bushehr University of Medical Sciences, Bushehr, Iran Mohammad Nicknam Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran 2024 11 30 2024 12 31 Human cytomegalovirus (HCMV) poses a significant challenge to vaccine development due to its complex biology characterized by latency, immune evasion strategies, and undefined correlates of protection (CoPs). HCMV latency allows the virus to evade immune surveillance by remaining in a quiescent state in host cells, with the risk of reactivation triggered by immune damage or cell differentiation. In addition, HCMV employs an arsenal of immune evasion strategies, including modulating MHC expression, inhibiting natural killer (NK) cell activity, and subverting antibody-mediated responses, so these mechanisms further complicate vaccine design. Despite these obstacles, advances in basic research in immunology and vaccine technologies offer new opportunities. Strategies such as targeting latency-associated mechanisms, using memory inflation of CMV-specific T cells to induce long-term tissue-resident immunity, and developing immunogens that antagonize viral immunoevasins are promising approaches. New platforms, including mRNA and vector-based vaccines, show the potential to elicit robust humoral and cellular responses against key viral antigens such as glycoprotein B, pentamer complex, and pp65. In addition, adjuvants that restore impaired NK and T cell function could improve vaccine effectiveness. This review examines the molecular and immunological barriers to HCMV vaccine development and highlights innovative approaches to address these challenges. By addressing the complexities of latency, immune evasion, and CoPs, we propose a roadmap for developing a multimodal vaccine that can provide effective and durable protection against HCMV infections. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4263 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4263/2183

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 551 562 Pengtao Song Department of Pathology, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou University, Huzhou, China Wei Mao Department of Respiratory and Critical Medicine, Huzhou Traditional Chinese Medicine Hospital, Affiliated to Zhejiang Chinese Medical University, Huzhou, China Yinan Chen Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, China Zhicong Liu Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, China Yi Chen Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, China 2025 02 10 2025 03 14 While vitamin D deficiency (VDD) is implicated in both asthma and osteoporosis, the synergistic mechanisms linking these comorbidities remain unexplored. This study introduces a novel murine model of VDD-induced concurrent asthma and osteoporosis, uniquely addressing their bidirectional exacerbation through NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and oxidative stress crosstalk. Female C57 mice were stratified into control, bronchial asthma (BA), osteoporosis (OP), BA+OP, and VDD+BA+OP groups, with therapeutic evaluation of low-dose (LD) and high-dose (HD) vitamin D supplementation. Unlike prior studies, our results demonstrate that VDD amplifies airway resistance and bone microstructural deterioration via NLRP3-driven pyroptosis (elevated cleaved caspase-1, N-terminal gasdermin D and suppressed antioxidant defenses (reduced glutathione peroxidase and catalase, and elevated malondialdehyde). Critically, HD supplementation reversed these effects more robustly than LD, restoring pulmonary compliance, trabecular integrity (bone volume/total volume: 0.0298 vs 0.0356 in VDD+BA+OP), and suppressing inflammasome activity. Mechanistically, we identify a feedforward loop wherein VDD-induced oxidative stress primes NLRP3 activation, which further exacerbates inflammation and bone resorption—a pathway uniquely mitigated by HD vitamin D. These findings provide the first evidence of HD vitamin D’s dual therapeutic efficacy in comorbid asthma-osteoporosis, offering a paradigm shift in targeting the NLRP3/oxidative stress axis for managing multifactorial inflammatory diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4339 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4339/2193

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 428 440 Sahar Rahimi Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran Zahra Sayevand Department of Physical Education, Malayer Branch, Islamic Azad University, Malayer, Iran Leli Rezaie Kahkhaie Department of Internal Medicine, Amir Al Momenin Hospital, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran Tayebeh Ahmadi Department of Medical Laboratory Science, College of Science, Knowledge University, Erbil, Iraq Atena Alifarsangi Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran 2024 11 04 2024 12 23 The COVID-19 pandemic has highlighted the essential role of a strong immune system in fighting infectious diseases. Understanding the relationship between exercise, physical activity, and immune function is crucial for recognizing how lifestyle factors can improve immune resilience. This review article aims to provide a comprehensive overview of the effects of exercise on the immune system during the COVID-19 pandemic. Additionally, it presents recommendations, guidelines, and considerations for engaging in physical activity during this period. Based on the literature review, there is some controversy regarding the effects of high-intensity exercise on individuals' immune systems, whereas moderate exercise is generally beneficial in almost all cases. Also, individuals experiencing severe COVID-19 symptoms or other acute illnesses should abstain from physical activity until recovery.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4233 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4233/2189

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 451 461 Lianlian Ji Department of Pediatrics, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China Liqun Lin Department of Pediatrics, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China Jian Ye Department Radiography, Ruian Maternal and Child Health Hospital, Ruian, Zhejiang, China Zhishu Li Department of Pediatrics, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China 2024 12 06 2024 12 30 Mycoplasma pneumoniae pneumonia (MPP) is a prevalent cause of respiratory infections in children, sometimes leading to pleural effusion (PE). This study aimed to identify risk factors and clinical features associated with PE in pediatric MPP patients. We conducted a retrospective case-control study involving 412 children with MPP and 82 with MPP+PE at the Third Affiliated Hospital of Wenzhou Medical University from January 2021 to January 2024. Demographic, clinical, and laboratory data were analyzed using multivariate logistic regression and receiver operating characteristic (ROC) curves. Significant findings included a higher incidence of immunocompromised states in the MPP+PE group (18.29% vs. 8.98%). At admission, children with MPP+PE exhibited higher respiratory rates (29.94 vs. 29.16 breaths/min), lower oxygen saturation (82.33% vs. 83.14%), longer fever duration (5.75 vs. 4.83 days), elevated white blood cell counts (WBC) (11.64×10^9/L vs. 10.12×10^9/L), and increased erythrocyte sedimentation rates (ESR) (20.66 vs. 19.49 mm/h). Patients with PE also experienced longer antibiotic treatment (9.14±4.91 vs. 7.46±3.29 days) and extended hospital stays (13.58±4.18 vs. 12.37±3.52 days). Multivariate analysis identified several significant predictors of PE, and a joint prediction model achieved an area under the curve (AUC) of 0.842, sensitivity of 0.796, and specificity of 0.793. These findings suggest that specific clinical and laboratory factors can help identify children at higher risk for PE, facilitating timely interventions. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4270 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4270/2191

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 462 471 Yihao Lin Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fujian, China Yuhai Hu Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fujian, China Zhou Zheng Fujian Abdominal Surgery Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China Minhui Chi Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fujian, China 2024 10 21 2025 01 14 Peripheral blood follicular helper T cells (Tfh) are essential in humoral immunity; however, their prognostic significance in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) is not well understood. This study aimed to evaluate the predictive value of Tfh cells for short-term prognosis in 200 HCC patients undergoing ICIs. A retrospective analysis categorized patients based on their clinical outcomes at six months post-treatment: those demonstrating improvement were classified as having a favorable prognosis (n=86), while those with no remission, deterioration, or death were classified as having a poor prognosis (n=114). Key prognostic factors assessed included C-reactive protein (CRP), interleukin-6 (IL-6), Tfh cell counts, and combination therapy. Significant associations were identified between progn 15 Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) plays a pivotal role in tumor immune evasion. The efficacy of these treatments is limited by variable patient responses and adverse effects. It is necessary for a deeper understanding of the underlying biological mechanisms. This study used a 2-step Mendelian randomization (MR) approach to investigate causal relationships among gut microbiota, lipid and amino acid metabolic traits, and PD-1/PD-L1. The summary statistics for 412 traits of the gut microbiome (N=7738), 249 traits of serum metabolites (N=115 078), and 2 traits of PD-1/PD-L1 (N=3301) were derived from publicly genome-wide association studies. The primary method employed for MR was inverse-variance weighted regression. We conducted a series of sensitivity analyses to evaluate the reliability of the causal estimates. Subsequently, mediation analysis was undertaken to elucidate the pathway from gut microbiome to PD-L1, mediated by serum metabolic markers. Our analyses identified 28 gut microbial traits significantly affecting PD-L1 and 14 affecting PD-1, 8 of which remained consistently linked to PD-L1 after sensitivity analysis. Furthermore, 13 serum lipid and amino acid metabolic traits exhibited significant causal effects on PD-L1, with 6 remaining robust post analysis. Notably, Bacteroides dorei demonstrated a causal effect on PD-L1, mediated 9.6% by the metabolic biomarker phenylalanine. These findings highlight the intricate interplay among gut microbiome, metabolic biomarkers, and immune regulation. They suggest novel therapeutic targets for cancer treatment that emphasize the value of microbiome and metabolic biomarkers in improving immunotherapy outcomes and promoting personalized medicine. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4629 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4629/2322

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 16 1 13 Jun Zhang Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Huijing Tong Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Xiaojun Wang Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Yingwei Ding Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Linghong Xu Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China Gang Chen Department of Emergency, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China 2025 12 10 2026 01 27 Sepsis is a life-threatening systemic inflammatory response syndrome marked by high mortality and immune dysfunction. Histamine, synthesized from histidine, by histidine decarboxylase (HDC), regulates immune cell recruitment and inflammatory mediators, playing a key role in inflammatory diseases. The precise mechanisms and clinical significance of histamine in sepsis require further study. Gene expression data from the Gene Expression Omnibus (GEO) database were analyzed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed histamine-related genes (DEHRGs). Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), were utilized to screen diagnostic genes, and a predictive model was constructed and validated using receiver operating characteristic analysis and decision curve analysis (DCA). Functional enrichment, immune infiltration assessment, using single-sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), regulatory network construction, and drug prediction were subsequently conducted. Nine DEHRGs were identified. Three key diagnostic genes-FYN, IL2RB, and MMP8-were selected and validated across multiple cohorts, showing high diagnostic accuracy (area under the curve [AUC]>0.85). The study revealed distinct immune patterns, including increased regulatory T cell (Treg) infiltration in the sepsis group. Two sepsis molecular subtypes with differential immune characteristics were also identified. This study systematically explored the association between histamine and sepsis pathogenesis, defining a three-gene diagnostic model and elucidating complex immune and molecular regulatory mechanisms. These findings offer new insights for developing targeted diagnostic and therapeutic strategies for sepsis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4694 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4694/2323

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 26 1 16 Jianping Jiang Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Shumin Li Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Mengqing Cao Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Haiqin Wang Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China Xiaoyan Jin Inpatient Service Center, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China 2025 08 20 2025 11 14 Bronchiectasis is a chronic respiratory condition characterized by persistent airway inflammation and recurrent infections, yet its underlying pathogenesis remains incompletely understood. This study aimed to investigate the roles of the lower respiratory tract microbiome and serum cytokine/chemokine profiles in the pathogenesis of bronchiectasis. In this retrospective study, we enrolled 285 bronchiectasis patients admitted to our hospital between January 2024 and June 2025. Participants were categorized into an acute exacerbation group (n=158) and a clinically stable group (n=127). We compared the two groups in terms of respiratory pathogens, immune function indicators (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, white blood cell count, and neutrophil count), pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A), anti-inflammatory cytokines (interleukin-10 and interleukin-4), acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A), and chemokines (monocyte chemoattractant protein-1). The involvement of these factors in disease pathogenesis was analyzed. Significant differences were observed between the groups in the rates of hypoalbuminemia, the presence of dyspnea and hemoptysis, and the oxygenation index in arterial blood gas analysis. Sputum cultures were positive in 103 (65.19%) patients in the acute exacerbation group, compared to 58 (45.67%) in the stable group. Immune markers CD3+, CD4+, CD8+, and the CD4+/CD8+ ratio were lower during acute exacerbation, while WBC and NEUT levels were elevated. Pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A) and acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A) were significantly higher during exacerbation, whereas anti-inflammatory cytokines (interleukin-10 and interleukin-4) were lower. Monocyte chemoattractant protein-1 levels were also elevated during exacerbation. Dysbiosis of the lower respiratory tract microbiome, immune dysfunction, and exacerbated inflammatory responses are interrelated and collectively contribute to the pathogenesis of bronchiectasis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4557 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4557/2330

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 30 1 17 Yonghui Zou Department of Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Yanqiu Wang Department of Anesthesia and Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Degao Liu Obstetrics and Gynecology Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China Changzhong Li Obstetrics and Gynecology Clinic, The People’s Hospital of Pingyi County, Linyi, Shandong, China Changling Li Obstetrics and Gynecology Clinic, The People's Hospital of Pingyi County, Linyi, Shandong, China 2025 08 07 2025 12 01 High risk human papillomavirus (HR-HPV) induced cervical intraepithelial neoplasia grade 1 (CIN1) is a low-grade lesion closely associated with persistent viral infection, and clinical management remains challenging. This study aimed to investigate clinical efficacy and immune response of recombinant human interferon α2b vaginal effervescent tablets in CIN1 caused by HR-HPV. In a retrospective study, 60 patients with HR-HPV and diagnosed with CIN1 from Shandong Provincial Hospital between December 2023 and December 2024 were divided into CT (n=30) and CR (n=30) groups, both groups were treated with conventional therapy, and recombinant human interferon α2b vaginal effervescent tablets were added to the CR group. The main assessment of both groups were inflammatory factor indicators, immune indicators, vaginal microenvironmental factors [hydrogen peroxide (H2O2) positivity, sialidase (SNA) positivity, leukocyte esterase (LE) positivity, N-acetylaminogalactosidase (NAG) positivity], HR-HPV conversion rate and clinical efficacy. Secondary outcomes included life quality scores, complication and adverse effect rates. After treatment, the indicators of both groups were significantly different from the pre-treatment. The changes in inflammatory indicators, immune indicators, SNA positivity rate, LE positivity rate, HR-HPV conversion rate, clinical efficacy, life quality, complications, and adverse reactions in the CR group were better than those in the CT group. No marked discrepancy was found in the comparison of H2O2 positivity rate and NAG positivity rate between both groups. Recombinant human interferon α2b vaginal effervescent tablets have significant therapeutic effects, as they alleviate inflammatory reactions, regulate immune indicators, and are worthy of clinical application and promotion. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4540 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4540/2334

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 06 1 13 EN Rahimeh Mohseni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Sara Soudi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Arezou Rahimi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Majid Sadeghizadeh Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Arezou Khosrojerdi Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2025 08 11 2025 12 28 Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to organ failure. This study examines the immunomodulatory effects of the M13 bacteriophage in a cecal ligation and puncture (CLP) mouse model of sepsis, comparing intravenous and intraperitoneal delivery routes. Key outcomes included cytokine responses, bacterial burden, organ injury, and survival. Sepsis was induced using the CLP model. M13 phages were verified by transmission electron microscopy and administered via IV or IP injection. Blood samples were collected at 24 hours, 72 hours, and day 5 for white blood cell, cytokine, and liver enzyme analysis. Bacterial burden was assessed by colony counts, liver injury by hematoxylin and eosin histology, and survival was monitored for 14 days. CLP induction caused marked increases in WBC counts, cytokines, C-reactive protein (CRP), bacterial load, and liver damage. Following phage treatment, inflammatory markers, bacterial burden, and tissue injury declined substantially. IV administration more effectively reduced systemic inflammation, whereas IP administration provided stronger protection of liver and kidney function and resulted in higher survival rates. M13 phage therapy demonstrates promising immunomodulatory and organ-protective effects in septic mice. The superior organ protection and survival benefits observed with IP delivery suggest potential translational value for targeted phage administration in sepsis management. Future studies should explore dose optimization, combination therapy, and mechanistic pathways to support clinical development. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4543 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4543/2335

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 17 1 13 Nima Jadidian Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Ali Hazrati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Arsalan yazdchi Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran Hamed Valizadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Reza Taban-Sadeghi Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Haleh Mikaeili Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran 2 Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2025 10 21 2026 01 25 The airflow limitation is one of the characteristics of chronic obstructive pulmonary disease (COPD), which is not entirely reversible. It seems that factors such as inflammation, hypoxia, and remodeling of pulmonary vessels can increase pulmonary hypertension (PH). This increase in pulmonary arterial hypertension leads to aggravation of disease complications. Considering the role of immune cells in causing pathological inflammation in the pathogenesis of COPD, it seems that Th17/Treg axis imbalance can be one of the main reasons for the difference in life expectancy in patients with COPD with and without PH. By measuring and comparing some inflammatory biomarkers in patients with COPD with and without PH, this study tries to introduce these biomarkers to predict the occurrence or nonoccurrence of this complication. This study aims to compare the ratio and activity of Th17 to Treg in patients with COPD with high (20 patients) and normal (20 patients) pulmonary arterial pressure. Five milliliters of blood containing anticoagulant were obtained to isolate peripheral blood mononuclear cells (PBMCs). Then, the ratio of Th17 to Treg, their number, and their activity were evaluated by ELISA, real-time polymerase chain reaction (PCR), and flow cytometry. Our results show that the amount of inflammatory factors and the population of Th17 cells in patients with COPD with PH is associated with a significant increase in PH compared to patients with COPD without PH, which