Toxicological Significances of Metallothionein: Induction by Inflammation

The biological roles of metallothionein (MT) in connection with defense systcins have been previously proposed. Some compounds in which toxicity is reduced by pre-synthesis of MT (e.g. some heavy metals and radical-producing compounds) can induce MT synthesis. Inflammation-producing compounds induce MT synthesis specific to the liver, rcduccd hy preadministration of glucocorticoid, and accompanied by the elevation of fibrinogen and ceruloplasmin in the plasma. MT inducing factor(s) for culturing hepatoma cells was detected in the serum of LPS-treated mice, and the presence of glucocorticoid at the physiological level was necessary for its MT-inducing activih. MT synthesis hy serum MT-inducing factor in cultured cells, and that by n-hexane administration in the liver were inhibited by the addition or preadministration of anti interleukin (IL)-6 antibody. In IL-6-transgenic micc. a high concentration of MT was observed specifically in the liver. These results show that MT synthesis by inflammation-p...