SYNERGISTIC INDUCTION OF METALLOTHIONEIN SYNTHESIS BY INTERLEUKIN-6, DEXAMETHASONE AND ZINC IN THE RAT

We investigated the reciprocal effects of interleukin-6 (IL-6), glucoc orticoid and zinc (Zn) on metallothionein (MT) synthesis in rats. MT s ynthesis in the liver, which is a key responsible organ in acute phase responses, was induced by IL-6 or dexamethasone (Dex), and in an addi tive manner by a combination of IL-6 and Dex 18 h after injection. MT synthesis in the lung and heart was evaluated by immunoassay using a s pecific antibody to MT-I, because of its low concentration in these ti ssues. Heart concentrations of MT-I were significantly increased by IL -6, and were further increased by the combination of IL-6 and Dex, alt hough Dex by itself had no effect. This suggests a synergistic effect of IL-6 and Dex on MT-I synthesis in the heart. A similar synergism wa s observed in the lung. To study the effect of Zn on the induction of MT and acute phase proteins, Zn, IL-6 and Dex were administered in var ious concentrations. The increase in liver MT induced by the combinati on of IL-6 and Dex with Zn (130 mu g MT/g of liver) was greater than t he sum of the increases induced by (IL-6 + Zn) and by (Dex + Zn) (103 mu g MT/g), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 a nd Dex depends on an adequate liver Zn content. Thus, the in vivo syne rgistic induction of acute phase proteins by IL-6, glucocorticoid and Zn may be required for the maximal and rapid response, not only in liv er but also in other tissues including heart and lung. This suggests t hat the synergistic reaction may be important for an enhancement of th e radical scavenging ability of tissues in acute phase responses. Copy right (C) 1996 International Society for Immunopharmacology