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Modulating asthma-COPD overlap responses with IL-17 inhibition
Leandro do Nascimento Camargo1,2, Renato Fraga Righetti1,2, Francine Maria de Almeida1
1Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.
Frontiers in Immunology
|November 15, 2023
Summary
Inhibiting interleukin-17 (IL-17) reduced airway hyperresponsiveness and inflammation in a mouse model of asthma-COPD overlap (ACO). This treatment also modulated cytokine production, extracellular matrix remodeling, and oxidative stress in the lungs.
Area of Science:
- Pulmonary Medicine
- Immunology
- Respiratory Research
Background:
- Interleukin-17 (IL-17) is a key mediator of inflammation and lung remodeling in asthma and COPD.
- Asthma-COPD overlap (ACO) presents unique challenges due to the combined pathologies of both diseases.
- Understanding IL-17's role in ACO is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic effects of anti-IL-17 monoclonal antibody treatment in a mouse model of ACO.
- To evaluate the impact of IL-17 inhibition on airway hyperresponsiveness, inflammation, and lung remodeling in ACO.
- To explore the modulation of specific signaling pathways and biomarkers by anti-IL-17 therapy in ACO.
Main Methods:
- An ACO mouse model was established using ovalbumin (OVA) and porcine pancreatic elastase (PPE) sensitization.
- Mice were treated with either anti-IL-17 monoclonal antibody or a saline control.
- Airway hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and lung tissue markers of inflammation, remodeling, oxidative stress, and signaling pathways were assessed.
Main Results:
- Anti-IL-17 treatment significantly reduced airway hyperresponsiveness (Rrs, Ers, Raw, Gtis) in ACO mice.
- Treatment led to decreased inflammatory cell counts (neutrophils, macrophages) in BALF.
- Inhibition of IL-17 attenuated various cytokines (IL-1β, IL-6, IL-13, IL-17, IL-33), matrix metalloproteinases (MMP-9, MMP-12), TGF-β, collagen type I, iNOS, and oxidative stress markers (8-iso-PGF2α).
- Signaling pathways including NF-kB, ROCK-1, and ROCK-2 were also attenuated by anti-IL-17 therapy.
Conclusions:
- Inhibition of IL-17 effectively modulates airway inflammation and hyperresponsiveness in an ACO mouse model.
- Anti-IL-17 therapy impacts lung tissue by reducing cytokine production, extracellular matrix remodeling, and oxidative stress.
- The findings suggest that targeting IL-17, potentially through modulation of NF-kB and FOXP3 pathways, is a promising therapeutic strategy for ACO.
Keywords:
anti-IL-17asthmaasthma-COPD overlap (ACO)extracellular matrix remodelinginflammationoxidative stressMore Related Videos
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