Cutaneous lewisite exposure causes acute lung injury

Area of Science:

• Toxicology
• Pulmonary Medicine
• Chemical Warfare Agents

Background:

• Lewisite is a potent vesicant and chemical warfare agent.
• Transdermal absorption of lewisite can lead to severe systemic toxicity.
• Understanding the pulmonary effects of lewisite exposure is critical for medical preparedness.

Purpose of the Study:

• To investigate the acute lung injury (ALI) induced by cutaneous lewisite exposure in a mouse model.
• To characterize the inflammatory and cellular changes in the lungs following lewisite exposure.
• To identify biomarkers associated with lewisite-induced lung damage.

Main Methods:

• Ptch1^+/- /SKH-1 mice were dermally exposed to varying doses of lewisite (2.5, 5.0, 7.5 mg/kg).
• Acute lung injury was assessed 24 hours post-exposure.
• Methods included arterial blood gas analysis, lung histology, cytokine profiling, bronchoalveolar lavage fluid analysis, and complete blood cell counts.

Main Results:

• Lewisite exposure resulted in hypercapnia and hypoxemia.
• Histological analysis showed dose-dependent inflammatory cell infiltration (neutrophils) and structural lung damage.
• Elevated levels of proinflammatory cytokines (IL-33, CXCL1, CXCL5, GCSF) and HMGB1 were observed in lung tissue and bronchoalveolar lavage fluid.
• Complete blood counts revealed eosinophilia and altered neutrophil-lymphocyte ratios, with increased mean platelet volume and RBC distribution width.

Conclusions:

• Cutaneous lewisite exposure induces significant acute lung injury in mice.
• The observed inflammatory markers and hematological changes are indicative of lewisite-induced pulmonary damage.
• These findings highlight the potential for lewisite exposure to cause mortality and underscore the need for effective countermeasures.