Activity of wool mill dust in vitro and in vivo; cytotoxicity, cytokine production, lymph node stimulation and histopathology

Dust collected from the air of wool mills in the North of England showed no significant toxic effect to rat alveolar macrophages or a human epithelial cell line in vitro. In contrast, macrophages stimulated in vitro with the dust released significant amounts of the pro-inflammatory cytokines Tumour Necrosis Factor (TNF) and Interleukin-1 (IL-1). Examination of the lung lymph nodes from rats exposed to wool dust showed an increased proliferative response. Possibly, alveolar macrophages, which had phagocytosed the dust and already had increased secretion of immunostimulatory cytokines, could be migrating to the lymph nodes and causing stimulation. However, transfer of a soluble stimulatory factor present in the dust, such as endotoxin, to the lymph node could also be responsible. Histological examination of the lung showed evidence of granuloma formation and fibrosis in airway walls. Our results suggest that symptoms of airway irritation described in wool mill workers, could not be explained by direct toxic effects on airway lining cells. These symptoms are more likely to be caused by stimulation of airway wall leukocytes in rats, leading to chronic inflammation.