IL-6 In Patients Research Articles

Investigation Role of IL-10 And IL-13 with Some Viral Species in Pathogenesis of Heart Diseases

Background; cardiovascular disease (CVD) is the most common cause of mortality and impairment. Atherosclerosis is the primary underpinning pathophysiology of CVD, but several variables could trigger it. The occurrence of it is linked to multiple risk factors related to metabolism, such as overweight and dyslipidemia. Objective; Detective predictive roles of IL-10 and IL-13 and positivity of viral infections in heart diseases. 60 blood samples were harvested (gel tube) from heart diseases patients who sleeping in hospital after diagnosis them by specialist physician.30 blood samples were taken from healthy individuals that labeled them as a control group. Interleukins (IL-10 and IL-13) and viral species (Parvovirus B19, SARS-CoV-2, HCV and HBV) were calculated by (ELISA). Present outcomes mentioned the most patients were males (71.7%) with age groups 51-60 (26.7%) and 61-70 (33.3%), ex-smokers (65.0%), and lean BMI (63.3%). Our investigation showed Parvovirus B19 scored highest positivity (15.0%), followed by HBV (6.7%), SARS-CoV-2 (5.0%), and then HCV (3.3%) in heart diseases patients with significant difference (p<0.05). Based on interleukins levels, present outcomes showed significant raised levels (p<0.05) of IL-10 and IL-13 in patients than control. ROC curve results showed the IL-13 scored highest sensitivity (80%) and specificity (84%) at cut off (>2.50) compared to IL-10 that showed highest sensitivity (81%) and low specificity (57%) at cut off (>9.50). Conclusions; gender, age and smoking are risk factors for heart diseases. Due to decreased immune state in patients, several viruses were discovered in those patients. IL-10 and IL-13 were raised in patients due to presence inflammation. IL-10 has paradoxical role (pro and anti-inflammatory) in pathogenesis heart diseases . IL-13 is more preferred in diagnosis heart diseases than IL-10 due to has (IL-13) highest sensitivity and specificity. Finally, there is no strong correlation between IL-10 and IL-13 in pathophysiology of heart diseases.

Regulation of plasma soluble receptors of TNF and IL-1 in patients with COVID-19 differs from that observed in sepsis

IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study. The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, IL1R1, IL1R2, TNFRSF1A, and TNFRSF1B expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients. Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened IL1R1 expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients. Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.

IL-17A, IL-17F and IL-23 in patients with rheumatoid arthritis

IL-17A, IL-17F and IL-23 in patients with rheumatoid arthritis

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

IL-22 in Atopic Dermatitis.

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by a multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due to the suboptimal efficacy of existing treatment options. Nonetheless, recent progress in elucidating the underlying mechanisms of the disease has facilitated the identification of new potential therapeutic targets and promising drug candidates. In this review, we summarize the newest data, considering multiple connections between IL-22 and AD. The presence of circulating IL-22 has been found to correlate with the severity of AD and is identified as a critical factor driving the inflammatory response associated with the condition. Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD.

Relationship between serum metabolic indexes and immune function in patients with insomnia and their mechanism

We conducted a study to examine how certain serum metabolic markers (reactive oxygen species (ROS), homocysteine (Hcy), and reduced glutathione (GSH)) impact the levels of IL-4 in patients with insomnia. The study involved 60 insomnia patients, including 20 with primary insomnia and 20 with somatopathy insomnia, aged 23-84 years with a mean age of 61.20 ± 12.59 years and a mean disease duration of 6.97 ± 8.45 years. There were 20 normal controls, 11 males and 9 females, aged 26-63 years, with an average age of 49.95 ± 10.52 years. We measured ROS levels using immunofluorescence, Hcy levels using enzyme-linked immunosorbent assay, and GSH levels using ELISA. The IL-4 level in serum was also detected by ELISA to assess the patient's immune function. Our analysis revealed that changes in ROS, Hcy, and GSH levels were associated with changes in IL-4 levels in serum. Therefore, early detection of serum metabolic changes in insomnia patients and proactive intervention can help reduce susceptibility to various infections and tumors.

Circulating MicroRNAs and Cytokines Associated with Celiac Disease.

The current research examines the molecular terrain of celiac disease (CD) through microRNA (miRNA) and cytokines as potential new diagnostic and therapeutic markers. Gluten-appropriate immune response is a key feature of an autoimmune clinical entity known as CD that leads to inflammation and degeneration of small intestine mucosa. However, the mechanisms responsible for this remain unclear. Quantitative reverse transcription polymerase chain reaction (RT-qPCR ) was carried out on serum samples obtained from patients with CD and control groups to unravel their pathogenesis. Assessing miR-155, miR-15b, interleukin (IL)-2, IL-7, IL-35and IL-37 levels in expression might be useful in diagnosing or treating the disorder. A significant dysregulation of these molecular players in patients with CD compared with healthy controls has been evidenced by results from this study. For instance, miR-155 was up-regulated, whereas miR-15b was significantly down-regulated in CD, illustrating their roles in immune responses and inflammation-mediated processes. Besides, there was an over-expression of IL-2 and an under-expression of IL-37 in patients with CD, indicating these biomolecules' role in immuno-dysregulation and inflammatory process underlying CD. In addition, a positive correlation between IL-2 and miRNA 155 expression levels was observed in patients with CD, suggesting that they could be involved together with other cytokines, showing the interplay between immune response pathways and inflammatory cascades during CD pathogenesis. These molecular signature discoveries might result in new and revolutionary diagnostic modalities and molecular-targeted therapies for CD pathogenesis. When used with the scientific understanding of miRNAs and cytokines associated with CD pathophysiology, it creates a basis for personalized medicine based on the individualized molecular profile of all patients. This will undoubtedly increase the efficacy of CD treatment strategies. In brief, more research on molecular pathways' workings should be done to harness their potential in CD diagnosis and treatment.

Altered gene expression of miR-155 in peripheral blood mononuclear cells of Multiple sclerosis patients: Correlation with TH17 frequency, inflammatory cytokine profile and autoimmunity

In the chronic, organ-specific autoimmune disorder known as multiple sclerosis (MS), the myelin sheath is attacked by immune cells, leading to damage to the central nervous system (CNS). It has been discovered that miRNAs are important in the etiology of MS, since deregulation of miRNAs can lead to defects in immune tolerance. In this study, we sought to investigate the involvement of miR-155 in MS disorder through examination of its altered expression in peripheral blood mononuclear cells (PBMCs) of patients with MS in compare with healthy controls. Furthermore, we investigated the frequency of T helper 17 cells (Th17) in MS patients and analyzed not only the expression of inflammatory cytokines including IL-6, IL-17 and IL-21 in patients’ PBMCs, but also their secreted levels in serum of patients suffering from MS. Subsequently, we assessed the correlation between miR-155 expression with Th17 frequency and levels of released cytokines in serum. Upregulated expression of miR-155 was detected in PBMCs of MS patients and the positive correlation between its expression with increased frequency of Th17 cells and their related inflammatory cytokine profile augmented secretion in serum were identified. In conclusion, our study revealed the significant association between Th17 frequency, increased level of cytokines related to Th17 differentiation and function with miR-155 augmented expression in PBMCs. So, our findings suggested that miR-155 and especially its expression in immune cells including effector T cells can be the target of future therapeutic strategies for the management and prevention of MS progression, however, further research is requisite before this approach can be utilized in clinical practice.

The Association of Serum Vitamin D With Anthropometric Indices, Lipid Profile, ICAM-1, and IL-17 in Patients Undergoing Coronary Artery Bypass Graft Surgery.

This study aimed to assess the relationship between serum levels of vitamin D with anthropometric indices, lipid profile and vascular inflammatory factors, in patients who candidate for coronary artery bypass grafting (CABG). This analytical cross-sectional study was conducted in patients who were candidate for CABG. Demographic information, medical records, anthropometric indicators, blood samples, and physical activity of 150 patients were collected. 146 participants with mean ± standard deviation of age: 61.8 ± 10.0 years and body mass index: 26.9 ± 3.7 kg/m2 completed the study. Based on serum levels of vitamin D, patients were divided into 2 groups; groups with sufficient (≥ 30 ng/mL) and insufficient amount of vitamin D (< 30 ng/mL). The 30.14% of the patients had serum vitamin D deficiency. Ejection fraction (EF) % between the 2 groups had significant difference. Unexpectedly the EF% increased 7% in patients with insufficient level of vitamin D (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.11; p = 0.001). Vitamin D status had a significant inverse association with body weight. The odds of vitamin D deficiency significantly increased by 4% with increasing one kg in weight (OR, 1.04; 95% CI, 1-1.08; p = 0.044). There were no significant association between serum vitamin D level and intra cellular adhesion molecule-1, interleukin-17, fasting blood glucose, and lipid profile (p > 0.05). Considering the inverse association observed between serum vitamin D with EF% and body weight, vitamin D may play a role in modulating of these indices.

Comparison of ozone therapy and routine medical treatment effect on disease severity and serum level changes of IL-33 in patients with remitting-relapsing multiple sclerosis: A parallelled randomised clinical trial

IntroductionIL-33 is an inflammatory cytokine involved in the pathogenesis of Multiple sclerosis (MS) as an autoimmune inflammatory disease. Ozone therapy has been shown to improve the symptoms of the disease in previous studies. Given the limitations of previous studies, we investigated the effect of adding ozone therapy to conventional medical treatment in remitting-relapsing multiple sclerosis (RR-MS) patients from the points of disease severity and blood levels of IL-33. MethodsThis clinical trial was performed on 66 RR-MS patients, among whom 55 finished the study. The patients were divided randomly into two groups; one group (intervention) received ozone therapy in addition to the routine medical treatment, and the other group (control) received only routine medical treatment. The level of IL-33 was measured by ELISA, and the severity of the disease was measured by an expanded disability status scale (EDSS) in all patients before and after the treatment. Finally, the relationship between the serum levels of IL-33 and EDSS score with the type of treatment was evaluated. The research project was registered at the International Center for the Registration of Clinical Trials in Iran (IRCT20171105037262N3). ResultsOur findings showed that the serum levels of IL-33 in the ozone plus medical-treated group significantly decreased compared to the medical-treated group (P<0.001). The EDSS score also decreased significantly in the ozone plus medical-treated group compared to the medical-treated group (P=0.019). ConclusionOzone therapy reduces the severity of RR-MS. Such an effect may be influenced by modifying IL-33 levels.

Investigation of Interleukine-1 Beta in Urinary Tract Infection Patients

Objective: The study aims to investigate interleukin -1 beta (IL-1 ) in patients with urinary tract infections in the holy governorate of Karbala. Methods: This study was conducted during the period from October 2023 to February 2024 at Imam Hussein Hospital in the holy city of Karbala and the laboratories of the College of Applied Medical Sciences/University of Kerbala. The current study included collecting urine samples (for use in general urine examination) and blood (using blood directly to measure the complete blood count CBC and serum to measure interleukin -1 beta (IL-1 ) from 70 patients with urinary tract infection (35 patients with positive bacterial growth and 35 patients with negative bacterial growth) in addition to 70 healthy people. The following general criteria were also investigated: age, sex, height, and weight. Results: Eight bacterial species were obtained. From the findings of the study is the increase in concentration of IL-1 in patients with urinary tract infections compared to the control group. The presence of a negative correlation between LBP and IL-1 . Conclusions: Increase the concentration of IL-1 in patients with urinary tract infections. There is a negative correlation in patients with bacterial growth between LBP and IL-1 .

Immunological and cytokine profile (IL-25 and IL-35) in patients with Entamoeba histolytica infection in Southern Iraq.

Amoebiasis is an intestinal disease caused by a unicellular parasite called Entamoeba histolytica. Interleukin-35 (IL-35) is the youngest specific member of the IL-12 family that plays a major role in the inhibitory function of regulatory T cells (Tregs) to curb inflammatory responses. IL-25 of the IL-17 family, which is widely released by Th2 cells and epithelial cells, is a warning signal produced upon cell or tissue injury to activate immune cells. The present study aimed to determine the cytokine profile (IL-25 and IL-35) in patients with E. histolytica infection in southern Iraq. This hospital-based study was conducted from August 2022 to May 2023. The study participants were patients with E. histolytica infection admitted to the infection department of general hospitals in Thi-qar province, southern Iraq. Initially, E. histolytica amebiasis was detected in the patients by nested multiplex PCR. All collected sera were tested with the Human Interleukin 35 (Biotech, China, Cat.RD-IL35-Hu) and IL25 (Biotech, China, Cat.RD-IL25-Hu) ELISA kits according to the instructions of the manufacturer. A total of 80 patients, including 50 patients with E. histolytica infection and 30 subjects in the control group without E. histolytica infection, were enrolled in the present study. The results showed a significant difference (p<0.001) in the serum level of IL-25 in patients with E. histolytica infection (4275.19 pg/mL) compared to individuals in the control group without E. histolytica infection (2186 pg/mL). Statistical analysis showed that there was no significant difference in the serum levels of IL-35 patients with E. histolytica infection compared with individuals in the control group without E. histolytica infection. The results of the present study show that the level of IL-25 is high in patients with E. histolytica infection. This indicates the important role of IL-25 in the activation of the immune system during intestinal inflammation. Therefore, this cytokine can be used as a diagnostic marker for E. histolytica infection.

The Impact of Serum Interleukin-4, Interleukin-10, Interleukin-17a, and Interleukin-22 Levels on the Development of Sporadic Ascending Aortic Aneurysms

Introduction: Aortic aneurysms are chronic diseases associated with inflammatory/immunological mechanisms. Interleukins (ILs) with pro-inflammatory and anti-inflammatory activities are shown to be related to the development of aortic damage. In this context, this study aims to evaluate the serum IL-4, IL-10, IL-17A, and IL-22 in patients with sporadic thoracic ascending aortic aneurysms. Patients and Methods: The population of this prospective study consisted of all consecutive patients with sporadic ascending aortic aneurysms who underwent thoracic aortic aneurysm repair between November 2019 and September 2022. In the end, 29 patients (the patient group) and 19 healthy voluntary participants without aortic pathology (the control group) were included in the study. The study’s primary outcome was the differences in serum IL levels between the groups. Results: The patient group was significantly older than the control group (p= 0.042). Significantly higher neutrophil-to-lymphocyte ratio (NLR) values were detected in the patient group (p= 0.031). The median IL10 (p= 0.001), IL-17A (p&lt; 0.001), and IL-4 (p&lt; 0.001) levels were significantly lower in the patient group than in the control group. There were no significant correlations between serum IL levels and the aneurysm diameter (p&gt; 0.05). On the other hand, there were moderate correlations between IL-10 and IL-17A (r= 0.409, p= 0.038), IL-10 and IL-22 (r= 0.464, p= 0.017), and IL-17A and IL-4 (r= 0.496, p= 0.006). NLR ≥1.95 was found to be an independent risk factor for sporadic ascending aortic aneurysms [Odds Ratio (OR)= 4.53, 95% confidence interval (CI)= 1.12-21.17, p= 0.040]. Conclusion: IL-10, IL-17A, and IL-4 were significantly lower in patients with sporadic ascending aortic aneurysms larger than 55 mm. NLR was an independent risk factor for sporadic ascending aortic aneurysms. The diameter of the aneurysm was not correlated with ILs. There were positive correlations between IL-10, IL-17A, and IL-4 levels.

Increased circulating interleukin-23 level in patients with sarcoidosis

BackgroundSarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. AimThis study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. Material and methodForty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. ResultsOf the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). ConclusionIn our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal. Although our results are somewhat contradictory to other studies in the literature, the question should still be whether sarcoidosis is a Th1/Th17 disease. Multicentre studies are needed in this regard.

Interleukin-37: associations of plasma levels and genetic variants in gout

ObjectivesIL-37 is an anti-inflammatory cytokine involved in inflammatory and autoimmune diseases. We aimed to investigate the association between IL-37 genetic variants, IL-37 plasma levels, and various clinical phases of gout.MethodsThe study included a control group with no history of primary hyperuricemia/gout, (n = 50), asymptomatic hyperuricemia (n = 74), intercritical gout (n = 200), acute gouty flare (n = 18), and chronic tophaceous gout (n = 30). Plasma IL-37 was analysed using enzyme-linked immunosorbent assay. All coding regions and intron–exon boundaries of IL-37 and exons 1–5 were amplified and sequenced.ResultsPlasma levels of IL-37 were significantly higher in asymptomatic hyperuricemic (p = 0.045), intercritical gout (p = 0.001), and chronic tophaceous gout (p = 0.021) cohorts when compared to control group. The levels of IL-37 in patients with acute gouty flare were comparable to control group (p = 0.061). We identified 15 genetic variants of IL-37: eight intron (rs2708959, rs2723170, rs2708958, rs2723169 rs2466448, rs3811045, rs3811048, rs2708944) and seven non-synonymous allelic variants (rs3811046, rs3811047, rs2708943, rs2723183, rs2723187, rs2708947, rs27231927), of which rs2708959 showed an over-presentation in gouty and acute flare cohorts (p = 0.003 and 0.033, respectively) compared to European population (minor allelic frequency MAF = 0.05) but not in control and hyperuricemic cohorts (p/MAF = 0.17/0.08 and 0.71/0.05, respectively).. On the contrary, rs3811045, rs3811046, rs3811047, and rs3811048 were underrepresented among individuals with tophaceous gout (MAF = 0.57) compared to European MAF 0.70–0.71, but not compared to the control cohort (MAF = 0.67).ConclusionsWe demonstrated the up-regulation of IL-37 levels across the clinical phases of gout: asymptomatic hyperuricemia, intercritical, and chronic tophaceous gout compared to control. Moreover, 15 genetic variants of IL-37 were identified and their associations with the clinical variants of gout were evaluated.

Pivotal Role of Serum IL-37 In Patients with Chronic HBV and HCV

Interleukin-37 (IL-37) is an anti-inflammatory cytokine that has an intrinsic role in many diseases through its extracellular and intracellular mechanisms. It was found to be in high concentrations in chronic diseases. In this study, the concentration of IL-37 was measured in 62 patients with chronic hepatitis C and 65 patients with chronic hepatitis B with 38 individuals as Healthy group using ELISA to confirm that IL-37 can be used a biomarker for hepatitis chronic diseases. Receiver operating characteristic (ROC) curves were used to support this hypothesis. IL-37 levels were significantly higher in viral hepatitis patients (Hepatitis C virus and Hepatitis B virus) than in controls (92.28 ± 47.5, 83.1±43.44, 42.8±12.14 ng/L), respectively with p= 0.00001. The ROC curve showed that all hepatitis patients (HCV and HBV) could be distinguished from the control group according to their levels of IL-37 with an AUC value for HBV was 0.886, while for HCV was 0.955. In addition, the cut-off value for IL37 in patients suffer from HBV was 58.55 ng/L with a sensitivity of 80% and a specificity of 100 %, while the cut-off value for IL37 in HCV patients was 57.27 ng /L with a sensitivity of 90% and a specificity of 97%. This study concluded there was an increase in the IL-37 concentration in patients with chronic HBV and HCV.

Assessment of Serum Interleukin-35 Levels in Iraqi Patients with Hepatitis C Virus Infection

Background: It is unclear how IL-35 contributes to chronic hepatitis C virus (HCV) infection. Objective: To evaluate the association of IL-35 with the viral load in HCV infections. Methods: Fifty patients were included, and their age and sex were matched with 50 healthy subjects. Seven ml of venous blood was obtained and tested for anti-HCV antibodies using the ELISA kit, quantitative measurement of HCV RNA by PCR, and estimation of serum levels of IL-35. Results: The HCV viral RNA titers ranged from 165 to 55595000 copies/mL and were positive for anti-HCV antibodies. The control group was negative. The serum level of IL-35 in the patients was significantly lower than in the controls. The correlation coefficient for HCV viral loads and IL-35 in patients is equal to 0.114. The serum IL-35 level was highest in the age group of 30–39 years. The HCV patients on treatment have a mean viral load equal to 406,3051.90 copies/ml and a mean IL-35 level equal to 151.98 ng/ml; those without treatment have a mean viral load equal to 765,525.94 copies/ml and an IL-35 level equal to 165.09 ng/ml. The gender distribution of HCV viral load revealed non-significant differences. Conclusion: Most of the HCV patients did not achieve rapid or sustained virologic responses after treatments. Serum IL-35 was significantly reduced and shows a weak positive correlation with HCV viral load. Older HCV patients usually had lower serum IL-35 levels.

Ki67-targeted oncolytic adenovirus expressing IL-15 improves intratumoral T cell infiltration and PD-L1 expression in glioblastoma

Glioblastoma (GBM) is a devastating malignant brain tumor. Current therapeutic strategies targeting tumor cells have limited efficacy owing to the immunosuppressive microenvironment. Previous work demonstrated that the targeted Ad5-Ki67/IL-15 could specifically kill tumor cells and decrease the angiogenic capacity in vitro. However, the efficacy of this virus in vivo and its effect on the tumor microenvironment (TME) has not been elucidated. In this study, we found that the Ad5-Ki67/IL-15 treatment down-regulated PD-L1 expression of glioma cells. More importantly, Ad5-Ki67/IL-15 also remodeled the tumor microenvironment via increasing intratumoral T cell infiltration and PD-L1 improvement in a GBM model, as well as the increase of antitumor cytokines, thereby improving the efficacy of GBM treatment. Furthermore, a combination of Ad5-Ki67/IL-15 with PD-L1 blockade significantly inhibits tumor growth in the GBM model. These results provide new insight into the therapeutic effects of targeted oncolytic Ad5-Ki67/IL-15 in patients with GBM, indicating potential clinical applications.

Cut-off values for IL-21 and IL-23 as biochemical markers for pemphigus vulgaris.

Pemphigus vulgaris (PV) is a potentially fatal mucocutaneous autoimmune disease characterized by severe skin lesions. Interleukin-21 (IL-21) and IL-23 have been linked to several autoimmune inflammatory diseases that may have a critical role in PV immunopathogenesis, including T-helper 17 (Th17) development. This study aimed to compare the serum levels of IL-21 and IL-23 in patients with PV and healthy controls. This case-control study included 90 participants (45 patients and 45 controls). Serum IL-21 and IL-23 were measured using the Sandwich-ELISA method provided by Sunlong Biotech, China. The findings revealed statistically significant results for IL-21 O.D. and Conc. (p=0.012*) and highly significant results for IL-23 O.D. and Conc. (p=0.000**). Furthermore, cut-off values were established for IL-21 (O.D.=0.071 pg/mL, Conc.=6.468 pg/mL) and IL-23 (O.D.=0.141 pg/mL, Conc.=6.745 pg/mL). These results indicate a potential association between PV and IL-21, IL-23, and the identified cut-off values. The particular roles of cytokines and how they can be utilized to treat PV require more investigation. To our knowledge, this was the first study to detect a cut-off point for IL-21 and IL-23 that may be used as novel and cost-effective biochemical markers for disease diagnosis.

The unified airway hypothesis: evidence from specific intervention with anti-interleukin-5 biologic therapy.

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and interleukin (IL)-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP] and non-steroidal anti-inflammatory drug exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision-making.