Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice

Area of Science:

• Pulmonary Medicine
• Toxicology
• Pathology

Background:

• Pulmonary fibrosis is a progressive lung disease with unknown causes and poor outcomes.
• Polyhexamethyleneguanidine phosphate (PHMG-P) exposure is linked to acute interstitial pneumonia and pulmonary fibrosis in humans.
• Previous studies showed sustained lung inflammation and fibrosis in rats after PHMG-P inhalation.

Purpose of the Study:

• To determine the time course of lung inflammation and fibrosis induced by PHMG-P.
• To compare the pathological effects of PHMG-P with bleomycin (BLM).
• To investigate the underlying mechanisms of PHMG-P-induced lung damage.

Main Methods:

• Mice received intratracheal administration of PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg).
• Inflammatory and fibrotic markers, along with inflammasome protein expression, were measured at weeks 1, 2, 4, and 10 post-instillation.
• Pathological changes, including immune cell infiltration, collagen deposition, fibroblast proliferation, and type II epithelial cell hyperplasia, were assessed.

Main Results:

• Inflammatory and fibrotic responses persisted for up to 10 weeks in the PHMG-P group and 4 weeks in the BLM group.
• Significant immune cell infiltration and collagen deposition were observed in lung tissues.
• NALP3 inflammasome activation was detected in the PHMG-P group up to 4 weeks, correlating with persistent inflammation and fibrosis.

Conclusions:

• A single exposure to PHMG-P induces sustained pulmonary inflammation and fibrosis for at least 10 weeks.
• PHMG-P-induced lung pathology shares similarities with humidifier disinfectant-associated lung injury.
• NALP3 inflammasome activation may drive the persistent inflammatory and fibrotic responses to PHMG-P.