Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

Area of Science:

• Nanotechnology
• Toxicology
• Pulmonary Medicine

Background:

• Carbon nanotubes (CNTs) show promise for drug delivery but can cause lung inflammation.
• Fibre characteristics influence CNT-induced pulmonary toxicity.
• Double-walled carbon nanotubes (DWCNTs) are a specific type with potential applications.

Purpose of the Study:

• To investigate the pulmonary response to DWCNTs in mice.
• To analyze inflammation, cellular uptake, and systemic effects.
• To identify design parameters for safer CNTs.

Main Methods:

• Intratracheal instillation of DWCNT suspensions in mice.
• Bronchoalveolar lavage (BAL) analysis.
• Cytokine profiling (BAL and blood).
• Lung antioxidant profiling.
• Light microscopy for cellular uptake.

Main Results:

• A 50 μg dose of DWCNTs induced significant, unresolved pulmonary inflammation over 7 days.
• Macrophages, not granulocytes, ingested DWCNT agglomerates.
• Increased macrophages, multinucleated macrophages, and lymphocytes indicated chronification.
• Pulmonary antioxidant depletion and systemic inflammation were observed.
• Neutrophil-driven acute inflammation shifted to macrophage/lymphocyte involvement after day 3.

Conclusions:

• High-dose DWCNT agglomerates cause acute pulmonary toxicity.
• Inflammation resolution was ineffective, suggesting chronification.
• Systemic effects include antioxidant depletion and inflammation.
• Findings provide insights for designing less toxic CNTs.