The Role of IL5 in Epithelial Cell Integrity
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Change in Innate immune inflammatory markers (ng/mL)
研究概览
简要总结
The goal of this laboratory study is the examine the effect of mepolizumab drug on the health and function of the cells lining the human nasal airways in vitro cell culture derived from patients with chronic rhinosinusitis with nasal polyposis. The main questions the study aims to study are:
- To see what mepolizumab does to suppress inflammation of the human cells.
- To see what mepolizumab does to maintain barrier integrity of epithelial cells
详细描述
The investigators hypothesize that anti-IL5 treatment will promote epithelial cell function by inhibition of Type 1 and innate immune mediated inflammation and epithelial-mesenchymal transition resulting from IL5 induction.
Aim 1. To test the hypothesis that anti-IL5 therapy results in inhibition of epithelial cell dysfunction including epithelial derived inflammatory responses and barrier dysfunction, the investigators will examine the effect of in vitro anti-IL5 mepolizumab exposure of human primary nasal epithelial cells from chronic rhinosinusitis with nasal polyposis on Type 1, Type 2 and innate immune inflammatory markers, and markers of epithelial cell barrier function.
Aim 2. To examine the effect of mepolizumab to broadly modulate the expression of Type 2, Type 1, Type 3, and innate immune inflammatory gene responses in human nasal airway epithelial cells, the investigators will perform high throughput RNA sequencing on IL5 primed differentiated human primary nasal epithelial cells exposed to the presence and absence of mepolizumab in vitro cell culture which are derived from patients with chronic rhinosinusitis with nasal polyposis. These studies will provide an unbiased approach to identification of biomarkers resulting from anti-IL5 treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) sinonasal inflammation for greater than 12 weeks which include at least 2 of the following symptoms: nasal obstruction/congestion, nasal discharge (anterior or posterior), facial pressure/pain, reduction of sense of smell.
- •(2) confirmation of the clinical symptoms by: (2a) CT scan evidence of paranasal sinus mucosal inflammation, and/or (2b) endoscopic exam evidence of purulence from the sinuses or ostiomeatal complex; and
- •(3) presence of nasal polyps seen on endoscopic exam or sinus CT scan.
排除标准
- •1. Children under the age of 18 will be excluded due to:
- •possible confounding diagnosis of cystic fibrosis and other non-Type 2 inflammatory etiologies that commonly presents with nasal polyps in the pediatric population.
- •lack of complete pneumatization of the majority of paranasal sinuses
- •2. pregnant or lactating females,
- •3. prisoners,
- •4. mentally disabled
- •5. persons unable to give informed consent will be contemplated for inclusion.
- •6. disease secondary to a clearly defined anatomic process, such as facial trauma, and obstruction due to sinonasal neoplasm.
- •7. exposure to oral or systemic IV glucocorticoids within 2 weeks of surgery
- •8. exposure to immunomodulatory biologics will be excluded. These include, but are not limited to systemic treatment with biologics omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, or rituximab.
研究组 & 干预措施
Mepolizumab treatment arm
Nasal epithelial cells will be exposed in vitro to mepolizumab in culture.
干预措施: Mepolizumab (Drug)
Control arm
Nasal epithelial cells will be exposed in vitro to media without mepolizumab in culture
结局指标
主要结局
Change in Innate immune inflammatory markers (ng/mL)
时间窗: 0 to 48 hours
IL1 receptor mRNA and protein expression
Change in epithelial barrier function protein expression (ng/mL)
时间窗: 0 to 48 hours
E-cadherin
Change in Type 1 inflammatory markers (ng/mL)
时间窗: 0 to 48 hours
IL8 cytokine mRNA and protein expression
Change in Type 2 inflammatory markers (ng/mL)
时间窗: 0 to 48 hours
IL5 and thymic stromal lymphopoietin cytokine mRNA and protein expression
Change in epithelial integrity markers (staining intensity units)
时间窗: 0 to 48 hours
alpha-smooth muscle actin protein expression
次要结局
未报告次要终点