Airway hyper-responsiveness in lipopolysaccharide-challenged common marmosets (Callithrix jacchus)

Area of Science:

• Respiratory physiology
• Translational medicine
• Non-human primate models

Background:

• Developing human-specific therapeutics for respiratory diseases requires animal models with high predictive value for human trials.
• Airway hyper-responsiveness (AHR) is a key indicator of respiratory disease and a target for therapeutic intervention.

Purpose of the Study:

• To investigate lung function parameters in marmoset monkeys (Callithrix jacchus) for detecting pharmacologically or provocation-induced AHR.
• To establish the common marmoset as a translational non-human primate (NHP) model for lipopolysaccharide (LPS)-induced lung inflammation.

Main Methods:

• Development of a custom lung-function device for precise aerosol delivery during measurements.
• Invasive plethysmography was performed on 12 anesthetized marmosets under baseline and methacholine (MCh)-induced bronchoconstriction conditions.
• Lung inflammation was induced via intratracheal LPS administration, followed by repeat lung function measurements.

Main Results:

• Lipopolysaccharide (LPS) challenge significantly reduced the provocative dose (PD) of methacholine (MCh) required to increase lung resistance (RL).
• Airway hyper-responsiveness (AHR) was demonstrated in LPS-treated marmosets compared to naive animals.
• Collected pulmonary data included lung resistance (RL), dynamic compliance (Cdyn), and mid-expiratory flow (EF50).

Conclusions:

• The common marmoset serves as a viable translational NHP model for studying LPS-induced lung inflammation and AHR.
• Lung function data from marmosets can support pre-clinical efficacy and safety testing of anti-inflammatory drugs.
• This model facilitates the development of novel therapeutics for human respiratory diseases.