Analysis of short-term efficacy and safety of the first subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis / 中华皮肤科杂志

Objective:To investigate short-term efficacy and safety of subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis (AD) .Methods:A retrospective study was conducted on clinical data from children who were diagnosed with moderate-to-severe AD and subcutaneously injected with dupilumab in Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from March 2021 to August 2021. Changes in the Eczema Area and Severity Index (EASI), itch Numeric Rating Scale (NRS) score, SCORing Atopic Dermatitis (SCORAD) index, and Dermatology Family quality of life Index (DFI) were analyzed before and 4 weeks after the first subcutaneous injection of dupilumab. Adverse events were collected during the first injection to the first follow-up visit at week 4 after the start of treatment. Normally distributed measurement indices were compared by using paired t test, non-normally distributed measurement indices were compared by using signed rank test, and logistic regression analysis was used to evaluate the effects of disease duration, eosinophil counts, IgE levels, personal and family history of allergic diseases on EASI50 (≥ 50% decrease in the EASI score) after dupilumab treatment. Results:A total of 39 children were enrolled in this study, including 21 males and 18 females. Twenty-one patients were aged 2 to < 6 years, 18 were aged 6 to < 18 years, and their median age ( Q1, Q3) was 65.0 (53.0, 111.0) months. Four weeks after the single-dose subcutaneous injection of dupilumab, 18 patients (84.85%) achieved ≥ 50% decrease in EASI score, 13 (60.61%) ≥ 75% decrease in EASI score; 18 (75.76%) experienced a decrease of ≥ 4 points in peak NRS, and 20 (81.82%) ≥ 3 points in peak NRS; the SCORAD score decreased by ≥ 50% in 15 (68.75%) patients, and by ≥ 75% in 7 (18.75%). Neither common adverse events such as conjunctivitis, skin infections, injection site reactions, nor serious adverse events were observed in any of the children from the first injection to the first follow-up visit at week 4. Logistic regression analysis showed no significant effect of the disease duration, eosinophil counts, IgE levels, personal or family history of allergic diseases on EASI50 (all P > 0.05) . Conclusion:A single-dose subcutaneous injection of dupilumab can markedly improve pruritus and severity of skin lesions in children with moderate-to-severe AD, and enhance the family quality of life, with favorable short-term safety.

Expression of interleukin-4 receptor in non-small cell lung cancer and its clinical significance / 肿瘤

Objective: To investigate the expression of interleukin-4 receptor (IL-4R) in peripheral blood of patients with non-small cell lung cancer (NSCLC) before and after surgical operation and its clinical significance. Methods: The expression levels of IL-4R in peripheral blood of 84 patients with NSCLC before and after surgical operation as well as in peripheral blood of 40 healthy volunteers were measured by real-time fluorescent quantitative-PCR and ELISA. The expressionsof IL-4R in NSCLC tissues and the corresponding para-cancerous tissues were detected by immunohistochemistry. The correlations of IL-4R expression with clinicopathological characteristics and prognosis were analyzed. Results: The expression levels of IL-4R in peripheral blood of patients with NSCLC before and after surgical operation were both higher than that of healthy volunteers. The expression level of IL-4R in peripheral blood of patients with NSCLC after surgical operation was lower as compared with that before surgical operation, but which was higher than that of healthy volunteers (all P < 0.05). The positive expression rate of IL-4R in NSCLC tissues was higher than that in the corresponding para-cancerous tissues (P < 0.05). The overall survival and disease-free survival of NSCLC patients with high expression of IL-4R mRNA were poorer than those of the patients with low expression of IL-4R mRNA (both P < 0.001). Tumor stage, recurrence, metastasis and IL-4R mRNA level were independent prognostic factors of NSCLC (all P < 0.05). Conclusion: IL-4R in peripheral blood of patients with NSCLC is up-regulated, and the expression level of IL-4R is one of the independent prognostic factors of NSCLC.

Effects of microRNA-155 on interleukin-1 receptor-associated kinase 1 and 4 mRNA expression in liver injury of endotoximia mice / 中国小儿急救医学

Objective To explore the protective effect of rnicroRNA (miRNA)-155 inhibitor on interleukin-1 receptor-associated kinase (IRAK)-1 mRNA and IRAK-4 mRNA in endotoximia induced liver injury in mice.Methods One hundred and twenty male BALB/c mice were randomly divided into healthy control group(n =40),endotoximia group (n =40) and miRNA-155 inhibitor group (n =40).Each group were divided into 6 h,12 h,24 h,48 h subgroups,each of which consisted of 10 mice.The mice in miRNA-155 inhibitor group were administered with miRNA-155 inhibitor[80 mg(kg ·d)] via tail vein injection before lipopolysaccharide (LPS) administration while the other two groups treated with normal saline,following 24 hours,model of endotoximia mice was produced by injection of LPS intraperitoneally.At 6 h,12 h,24 h,48 h after LPS exposure,the experimental mice were sacrificed and the liver tissue samples were collected.Histopathological changes,the expression of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,tumor necrosis factor (TNF)-α,IL-1,IL-10 were detected.Results LPS exposure resulted in increase of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,TNF-α,IL-1 and IL-10 in both endotoximia group and miRNA-155 inhibitor group compared to the control group,miRNA-155 inhibitor resulted in decrease of miRNA-155,IRAK-1 mRNA,IRAK-4 mRNA,TNF-α,IL-1 and IL-10 in miRNA-155 inhibitor group compared to the endotoximia group.There were significant differences of miRNA-155 expression at 12 h,24 h,48 h after LPS exposure among 3 groups (P ＜ 0.05).Both IRAK-1 mRNA and IRAK-4 mRNA showed significant differences at 12 h,24 h,48 h.Turning to inflammation factors,differences were found among 3 groups at all time points (P ＜ 0.05).At light-scope,there was improvement in sepsis associated liver injury in miRNA-155 inhibitor group compared to endotoximia group.Conclusion miRNA-155 inhibitor administration appears to down regulate IRAK-1 mRNA and IRAK-4 mRNA expression and further deduce the excessive inflammatory and anti-inflammatory reaction,which may alleviate liver injury in endotoximia mice.

Polymorphism of interleukin (IL)-4 receptor is associated with the risk and the prognosis of epithelial ovarian cancer in Korean women / 부인종양

OBJECTIVE: The aim of current investigation was to analyze the association between a single nucleotide polymorphism (SNP) in interleukin (IL)-4R Ile50Val and epithelial ovarian cancer (EOC) susceptibility and its prognosis in Korean women. METHODS: The blood samples of 98 EOC patients and 321 cancer-free control subjects were collected. Polymorphisms in IL-4R Ile50Val were determined using TaqMan method. Allele frequency and genotype distribution in the EOC group were compared with those of the control group. Thereafter association between this polymorphism and clinicopathologic factors such as stromal invasion, histologic type, surgical stage, and survival within the case group was evaluated. RESULTS: In the EOC group, the frequency of Ile allele was 52.0% which is significantly higher than that of the control group, 46.3% (p=0.014).There was significantly elevated risk of EOC in patients with Ile allele, with Odds Ratio of 2.49 (Ile/Ile+Ile/Val versus Val/Val, 95% Confidence Internal: 1.34-4.59). In subgroup analysis within the cancer group, this polymorphism showed no significant difference in clinicopathologic parameters such as stromal invasion, histologic type, and surgical stage. However the survival analysis showed the poor survival in the patients with Val/Val genotype. CONCLUSION: IL-4R Ile50Val polymorphism is associated with the susceptibility and the survival of EOC in Korean women.

Essential roles for ID-1 motif of interleukin-4 receptor alpha chain in interleukin-4 signaling / 천식및알레르기

BACKGROUND: Interleukin (IL)-4 is a pleiotropic cytokine that plays an important role in the pathogenesis of the allergic inflammation and asthma. Upon IL-4 receptor (IL-4R) engagement, a variety of signaling mediators, such as JAK kinases and STAT-6 are activated, leading to induction of IL-4 target gene expression including CD23 and germline C epsilon transcription. The function of a membrane-proximal domain of IL-4Ra, termed ID-1, remains to be characterized to date. OBJECTIVE: To assess whether the ID-1 domain mediates the induction of IL-4 target gene expression in a STAT-6-dependent manner. METHODS: The intracellular region of IL-4Ralpha was translationally fused to the extracellular region of IL-2Rbeta to provide ligand specificity to IL-2. Acidic amino acids and serine residues in the ID-1 domain of the chimeric receptor were substituted by site-directed mutagenesis. These receptor cDNAs were stably transfected to M12.4.1 murine B lymphoma cells. Following IL-2 stimulation, wild type and mutant clones for the ID-1 motif were subjected to FACS. RNA blotting and elecroporetic mobility shift assays to address the levels of CD23, germline C epsilon and STAT-6 inductions, respectively. RESULTS: ID-1 mutant clones were defective in gene induction of CD23 and germline C epsilon in response to IL-2 stimulation, as compared with wildtype clones. Moreover, IL-2-mediated STAT-6 activation was abolished in ID-1 mutant clones. CONCLUSION: These results demonstrate that the ID-1 domain of IL-4Ra is essential to induce IL-4 target gene expression through a STAT-6-dependent pathway.

Expression of Cell Surface Receptors on Human Glioblastoma Xenograft Model in NOD/SCID Mouse / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To obtain basic data for development of a glioblastoma-specific immunotoxin, the expression of variable cell surface receptors on a human glioblastoma xenograft model was evaluated, using NOD/SCID mice. MATERIALS AND METHODS: We developed a xenograft model in NOD/SCID mice implanted with a human glioblastoma cell line (U-87MG). Immunohistochemical studies were performed on implanted tumor nodules (n=8) using antibodies against CD71, EGFR, IGF-IRalpha, CXCR4 and IL-4Ralpha. RESULTS: Expression of IL-4Ralpha, in implanted tumornodules, was the highest of the cell surface receptors evaluated in this study. However, the endothelial cells in, and around, the tumor nodules also revealed immunopositivity against IL-4Ralpha. The immunoreactivity of IL-4Ralpha, and other surface receptors such as CD71, IGF-IRalpha and EGFR, was prominent in tumor nodules associated with tumor necrosis. CONCLUSION: IL-4Ralpha would be a possible target for the development of glioblastoma-specific immunotoxin, although there are limitations due to its endothelial expression.

Inhibition of Murine Allergic Response by Monoclonal Interleukin-4 Receptor Antibody

BACKGROUND AND OBJECTIVES: Several strategies were used to control the IgE production by interfering the functional activities of IL-4. However, most of them revealed limited effects to reduction of allergic response. This study was aimed to investigate the effects of interleukin-4 receptor (IL-4R) antibody on allergic response in animal model of allergic rhinitis. MATERIALS AND METHODS: Male BALB/C mice were sensitized with intraperitoneal injection of ovalbumin (OVA). IL-4R antibody was injected intravenously before intranasal challenge of OVA with ultrasonic nebulizer. Allergic symptoms, a number of eosinophils in nasal mucosa and serum level of OVA-specific IgE were evaluated. RESULTS: In IL-4R antibody treated mice, allergic symptom score were decreased (53.5%) than in control mice. The number of eosinophils in nasal mucosa were also reduced (47.4%). However, serum level of OVA-specific IgE were not obviously reduced (14.3%). CONCLUSION: These results suggested that IL-4R antibody has a potential effect for the treatment of allergic rhinitis in vivo.