Role of Respirable Saudi Arabian Sand and Pyridostigmine in the Gulf War syndrome: An Autoimmune Adjuvant Disease.

摘要

In the Lewis rat, inhalation of silica (SL) in realistic doses for 6 wk exacerbated the Mycobacterium- induced autoimmune adjuvant disease and impaired the humoral as well as cellular immune responses. In addition to the lung, significant SL deposition was observed in the spleen and the brain. In the lung, SL exposure resulted in granulomatous and fibrogenic changes, and decreased airway hyperresponsiveness. In addition to the increased number and changes in the surface phenotype, alveolar macrophages exhibited strong anti- apoptotic responses. The bronchoalveolar lavage fluids had moderate (metalloproteinase-9) to highly significant (metalloproteinase-2) increases in extracellular matrix digesting enzyme activities. We also observed that the anti-nerve gas agent, pyridostigmine bromide (PB), affected the immune system only when it was administered directly into the brain, indicating that PB and other cholinergic agents are unlikely to affect the immune response unless they cross the blood-brain-barrier. Future experiments will be directed to understand the mechanism of anti- apoptotic responses in alveolar macrophages. This response may be crucial for the development of SL- induced lung pathology. In addition, experiments are planned to ascertain the mechanism and the effects of SL sequestration in the brain.