Induction of acute lung injury after intranasal administration of toxin botulinum a complex.
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.
Taysse
L
L
Centre d'Etudes du Bouchet (Defense Research Center) BP No. 3, 91710 Vert le Petit France. laurent.taysse@dga.defense.gouv.fr
Daulon
S
S
Calvet
J
J
Delamanche
S
S
Hilaire
D
D
Bellier
B
B
Breton
P
P
D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008124:Locomotion / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors; D014121:Toxoids / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity
D001428:Bacterial Vaccines; D014121:Toxoids; D019274:Botulinum Toxins, Type A