Airway Delivery of Encapsulated Cytokine-Secreting Cells for Local Immunomodulation in Inflammatory Lung Diseases.

Summary

A modular, airway-deliverable microcapsule platform enables localized, durable release of IL-10 or IL-1Ra, attenuating inflammation in a rodent ARDS model and improving hypoxemia and structure in pulmonary fibrosis. Single-cell RNA-seq shows myeloid reprogramming, and large-animal testing supports safety, highlighting translational potential for ARDS and other inflammatory lung diseases.

Key Findings

• Airway-delivered microcapsules enabled localized, durable delivery of IL-10 and IL-1Ra in the lung.
• In a rodent ARDS model, localized IL-10 or IL-1Ra reduced inflammatory signaling and injury.
• Single-cell RNA sequencing showed IL-10 capsules reprogrammed myeloid composition and suppressed pro-inflammatory genes.
• In a bleomycin model, sustained IL-10 delivery improved hypoxemia and rescued lung architecture.
• Large-animal studies supported safety and biocompatibility of the airway-delivered capsules.

Clinical Implications

Not yet practice-changing, but supports a therapeutic avenue for localized anti-inflammatory treatment in ARDS to avoid systemic adverse events; informs design of first-in-human trials (dose, durability, airway delivery).

Limitations

• Preclinical study; no human efficacy data yet and not peer-reviewed (preprint)
• Long-term safety, dosing, and retention kinetics in diseased human lungs remain undefined

Future Directions

Proceed to GLP toxicology, device–procedure optimization for bronchoscopic delivery, and phase 1 trials focusing on safety, pharmacodynamics, and biomarker-guided dose in ARDS.