Blocking effect of anti-mouse interleukin-6 monoclonal antibody and glucocorticoid receptor antagonist, RU38486, on metallothionein-inducing activity of serum from lipopolysaccharide-treated mice

Although there is much evidence to suggest that lipopolysaccharide (LPS)-induced elevation of hepatic metallothionein (MT) contents is mediated by cytokines, the presence of MT-inducing activity in the serum of LPS-treated animals has not been examined, It was found that serum from LPS-treated mice stimulated MT induction in a hepatoma cell culture. The MT-inducing activity in serum was highest 2 h after LPS injection. Tumor necrosis factor and interleukin (IL)-6 levels in the serum were highest 1 and 2 h, respectively, after LPS injection. Anti-mouse IL-6 monoclonal antibody neutralized MT-inducing activity in serum obtained from mice 2 h after LPS injection, The MT-inducing activity in serum was blocked by the glucocorticoid antagonist, RU38486. A similar requirement for glucocorticoid was also observed in an IL-6-stimulated culture. These results show that the LPS-induced elevation of hepatic MT is mediated by IL-6, and the expression of the stimulating activity of IL-6 is dependent on the presence of glucocorticoid.