Nitric oxide and proinflammatory cytokines in the bronchoalveolar lavage fluid of rats after intratracheal instillation of toxic Stachybotrys chartarum spores.
Rao CY; Hirvonen MR; Burge HA; Brain JD
Am J Respir Crit Care Med 2001 Apr; 163(5)(2)(Suppl):A177
Rationale: There has been increasing concern regarding inhalation exposure to the fungus Stachybotrys chartarum. The fungus can produce potent mycotoxins that are thought to be the causative agents. We investigated the mechanisms of pulmonary injury and the role of mycotoxins using a rat model. Methods: Rats were intratracheally instilled one time with unaltered S. chartarum spores suspended in saline at 4 spore concentrations (2x10^6 to 2x10^7 spores/ml). The experiments were duplicated with spores that had been extracted in methanol to reduce the mycotoxin content. One day after instillation, the rats were sacrificed and the lungs lavaged. In a third experiment, rats were instilled with 2x10^7 spores/ml and a lavage was performed at 0, 6, 24 and 72 hours post-instillation. Nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) were measured in the lavage fluid. Results: At 24 hours, there was no change in IL-6 levels at any dose with the unaltered or methanol-extracted spores. TNF-a increased while NO levels decreased in a dose-dependent manner with both unaltered and methanol-extracted spores. For the unaltered spores, NO levels peaked at 6 hours (1.3 +/- 0.5 uM); TNF-a levels at 24 hours (142 +/- 44 pg/ml); IL-6 levels at 72 hours (123 +/- 99 pg/ml). Conclusions: In this animal model, mycotoxins playa dose-dependent role in pulmonary inflammation and injury. The responses from instillation of methanol extracted spores indicated that there may be components other than mycotoxins, integral to S. chartarum, that may also induce pulmonary effects.
Fungal-diseases; Fungi; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system-disorders; Laboratory-animals; Animal-studies; Lung-irritants; Lung-disease
American Journal of Respiratory and Critical Care Medicine. Abstracts of the American Thoracic Society 2001 International Conference, May 18-23, 2001, San Francisco, California