Cold Exposure Exacerbates Allergic Airway Inflammation via Ferroptosis: Evidence from a Murine Model

Area of Science:

• Pulmonary immunology
• Cellular biology
• Environmental health

Background:

• Extreme weather is linked to allergic airway inflammation (AAI).
• The mechanism, particularly ferroptosis (iron-dependent cell death), is unclear.
• Ferroptosis plays a role in lung diseases.

Purpose of the Study:

• Investigate if cold exposure aggravates OVA-induced AAI by promoting ferroptosis.
• Evaluate the protective effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1).

Main Methods:

• Established a murine AAI model with OVA sensitization and challenge.
• Exposed mice to cold (4°C or 10°C) daily.
• Assessed ferroptosis markers, iron, lipid peroxidation, antioxidants, and mitochondrial damage.
• Administered Fer-1 and analyzed airway inflammation, lung function, and histology.

Main Results:

• Cold exposure worsened AAI, increasing Th2 cytokines, impairing lung function, and enhancing airway remodeling.
• Cold induced ferroptosis, indicated by altered marker levels, increased iron/MDA, reduced GSH, and mitochondrial damage.
• Fer-1 treatment mitigated AAI severity and ferroptosis markers.

Conclusions:

• Cold exposure exacerbates AAI by inducing ferroptosis in lung tissues.
• Ferroptosis inhibition attenuated cold-induced AAI aggravation.
• Targeting ferroptosis offers a potential therapeutic strategy for AAI under cold conditions.