Effects of tetrandrine on macrophage production of cytokines resulting from silica or bleomycin exposure.
Ma-JYC; Barger-MW; Ma-JKH; Castranova-V
Toxicologist 1996 Mar; 30(1)(Part 2):139
Alveolar macrophage (AM) derived cytokines including interleukin-1 (IL1) and tumor necrosis factor-a (TNF-a) play an important role in the development of pulmonary fibrosis. Tetrandrine (TT) has been shown previously to reduce silica-induced pulmonary cell damage and collagen formation. The present objective was to investigate the effects of TT on AM production of IL-1 and TNF-a in response to silica or bleomycin (BLM). AM exposed to silica in vitro exhibited increased release of IL-1 and TNF-a. This increase was effectively reduced in the presence of TT. For in vivo studies, rats were intratracheally instilled with saline as control, 20 mg silica, or 1 mg/kg BLM. TT was administered orally (18 mg/kg) twice before exposure and 3 times/ week after exposure for desired time periods. These studies showed that in vivo exposure to silica or BLM yielded AM which produced elevated levels of IL-1 and TNF-a in culture. This production was inhibited by oral treatment with TT. These results indicate that TT treatment inhibits the silica- or BLM- stimulated production of IL-1 and TNF-a. These effects may explain in part the ability of TT to decrease silica induced fibrosis.
Silica-dusts; Silicates; Fibrosis; Pulmonary-system-disorders; Cell-damage; Collagen-fibrils; In-vitro-studies; In-vitro-study; In-vivo-study; In-vivo-studies; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California