The Role of IL5 in Epithelial Cell Integrity

The Role of IL5 in Epithelial Cell Integrity

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:

1. To see what mepolizumab does to suppress inflammation of the human cells.
2. To see what mepolizumab does to maintain barrier integrity of epithelial cells

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.

Inclusion Criteria:

• (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.

Exclusion Criteria:

• 1. Children under the age of 18 will be excluded due to:

  1. possible confounding diagnosis of cystic fibrosis and other non-Type 2 inflammatory etiologies that commonly presents with nasal polyps in the pediatric population.
  2. 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.