Changes in lymphocyte function and lung histology during the development of asbestosis and silicosis in the mouse

In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibers were removed by washing, no inhibition was observed. Moreover, actual stimulation of proliferation was noted when PG production was inhibited in vitro with indomethacin. In contrast, in vivo treatment of asbestos-instilled mice with indomethacin had no effect on the development of lung pathology.