# IL-1 receptor blockade as a novel treatment for exacerbation of allergic airway responses in humans

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $301,726

## Abstract

Asthma is a common chronic illness with higher rates of hospitalization for exacerbation than
many other chronic conditions. Standard treatment for acute asthma includes systemic
corticosteroids to suppress inflammation. However, the benefits of systemic steroids are not
effective for several hours after administration and do not target neutrophilic inflammation, a
shared feature of both viral- and allergen-induced exacerbations. Currently there is an urgent
need for treatments that work quickly and effectively in acute asthma exacerbations,
characterized by increased airway hyper-reactivity, neutrophilic and eosinophilic inflammation,
and mucous secretion with impaired clearance. We hypothesize that parenteral interventions
targeted at inflammatory cytokines implicated in acute asthma may prove to be useful adjuncts
to standard treatment of exacerbations. Our studies with allergic asthmatics have shown
enhanced airway IL-1β responses after exposure to pollutants. Numerous studies in murine
models of allergic asthma indicate that IL-1β is a central mediator of airway reactivity,
granulocyte recruitment, mast cell activation, and mucus hypersecretion; however, the exact
source of IL-1β has yet to be elucidated. Thus, IL-1 blockade presents a novel and targeted
strategy to treat broad features of an exacerbation. Anakinra is a FDA-approved IL-1 receptor
antagonist with a fast onset of action and short half-life. We have successfully and safely used
anakinra in reducing neutrophilic airway inflammation after environmental endotoxin challenge
in healthy volunteers. Using a model of inhaled allergen challenge frequently used to test novel
asthma therapies, we will test the central hypothesis that IL-1 blockade with anakinra will reduce
three features of asthma exacerbations in subjects with allergic airway disease: airway
hyperreactivity, inflammation, and mucous secretion and clearance. Aim 1 will test if IL-1
blockade mitigates allergen-induced bronchial reactivity. Aim 2 will test if IL-1 blockade
mitigates allergen-induced bronchial inflammation. Aim 3 will test if IL-1 blockade mitigates
allergen-induced mucus secretion and slowed clearance. We will be the first to determine if
anakinra alleviates these key features of asthma exacerbations using two dosing schemes that
reflect potential asthma rescue regimens. These proof-of-concept studies are essential to the
development of well-designed clinical trials that can test if this therapy is a useful adjunct in
exacerbations of respiratory disease for use in emergency care settings.

## Key facts

- **NIH application ID:** 10206234
- **Project number:** 5R01HL135235-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Michelle Hernandez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $301,726
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206234

## Citation

> US National Institutes of Health, RePORTER application 10206234, IL-1 receptor blockade as a novel treatment for exacerbation of allergic airway responses in humans (5R01HL135235-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10206234. Licensed CC0.

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