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Published on: July 6, 2019
Induction of acute lung injury after intranasal administration of toxin botulinum a complex
1Centre d'Etudes du Bouchet (Defense Research Center) BP No. 3, 91710 Vert le Petit France. laurent.taysse@dga.defense.gouv.fr
Abstract:
The inhalation of aerozolized botulinum toxin may represent a potential significant hazard to both military and civilian personnel. Since the lung is the primary target organ for inhaled toxin, the investigation reported herein was conducted to examine lung function in mice exposed to botulinum toxin A complex by intranasal route. Data includes lethality, symptomatology, measurement of respiratory function (minute ventilation, respiratory frequency, and tidal volume), and histopathology of the lungs. The clinical signs of intoxication are similar to those observed in foodborne botulism. Plethysmography revealed severe impairment of all respiratory parameters tested from 7 hours postexposure. Severe lung lesions, possibly secondary to the intoxication, were observed in mice who survived 14 days after the toxin challenge. These included intra-alveolar hemorrhage and interstitial edema. Mice immunized by the pentavalent (ABCDE) toxoid were protected against the neurotoxin (4 LD50) as revealed by the decrease of lethality and severity of nervous signs of intoxication, but not against histopathological changes in the lungs. These effects are nonspecific and require further experiments in order to specify the relationships between the pathology and the inflammatory process in the lung due to mediators such as cytokines,and possibly permanent physiological sequelae.
Insights
Inhaled botulinum toxin A severely impairs respiratory function in mice, causing lung damage. While immunization reduces lethality, it doesn't prevent lung pathology, indicating a complex inflammatory response.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Immunology
Background:
- Inhaled botulinum toxin poses a significant risk to military and civilian populations.
- The lungs are the primary target organ for inhaled botulinum toxin.
Purpose of the Study:
- To investigate lung function and pathology in mice exposed to aerosolized botulinum toxin A via intranasal administration.
- To assess the protective effects of pentavalent toxoid immunization against botulinum toxin A-induced lung injury.
Main Methods:
- Mice were exposed intranasally to botulinum toxin A complex.
- Respiratory function (minute ventilation, respiratory frequency, tidal volume) was measured using plethysmography.
- Lethality, clinical signs, and lung histopathology were evaluated.
Main Results:
- Intranasal botulinum toxin A exposure caused severe impairment of respiratory parameters starting 7 hours post-exposure.
- Histopathological examination revealed intra-alveolar hemorrhage and interstitial edema in surviving mice.
- Pentavalent toxoid immunization reduced lethality and neurological symptoms but did not prevent lung histopathological changes.
Conclusions:
- Inhaled botulinum toxin A causes significant respiratory dysfunction and lung injury in mice.
- Immunization provides protection against neurotoxicity but not against toxin-induced lung pathology.
- Further research is needed to understand the inflammatory mechanisms and potential long-term sequelae of botulinum toxin A lung exposure.
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