Assessment of mustard vesicant lung injury and anti-TNF-α efficacy in rodents using live-animal imaging.

Abstract

Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophage-dominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF-α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM-induced lung injury in rodents and assess the efficacy of anti-TNF-α antibody in mitigating toxicity. Anti-TNF-α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate-buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1-28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high-signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti-TNF-α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.

• Authors: Alexa Murray, Andrew J Gow, Alessandro Venosa, Jaclynn Andres, Rama Malaviya, Derek Adler, Edward Yurkow, Jeffrey D Laskin, Debra L Laskin
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1480 Issue 1 Pg. 246-256 (11 2020) ISSN: 1749-6632 [Electronic] United States
• PMID: 33165947 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2020 New York Academy of Sciences.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Irritants
• Tumor Necrosis Factor-alpha
• Mechlorethamine

Topics

• Acute Lung Injury (chemically induced, diagnostic imaging, drug therapy, metabolism)
• Animals
• Antibodies, Monoclonal, Murine-Derived (pharmacology)
• Irritants (poisoning)
• Magnetic Resonance Imaging
• Male
• Mechlorethamine (poisoning)
• Pulmonary Fibrosis (chemically induced, diagnostic imaging, drug therapy, metabolism)
• Rats
• Time Factors
• Tomography, X-Ray Computed
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)