Interleukin-1--stimulated induction of ceruloplasmin synthesis in normal and copper-deficient rats

Regulation of ceruloplasmin synthesis by interleukin-1 (IL-1) as influenced by dietary copper status was examined in rats. In copper-sufficient rats, ceruloplasmin oxidase activity did not peak in the serum until at least 24 h after IL-1 was given. The rates of ceruloplasmin synthesis, as measured by pulse labeling with [3H]leucine and immunoprecipitation, peaked 12 h after IL-1 and returned to basal rates by 24 h. Copper had to be given to copper-deficient rats for the IL-1 to induce oxidase activity. This activity was stimulated by copper alone in the deficient rats but not to the same level as with IL-1 plus copper. Copper alone did not increase the synthesis rate. IL-1 alone stimulated the synthesis rate without increasing the oxidase activity in the copper-deficient rats. The induction pattern of ceruloplasmin synthesis by IL-1 was the same in the copper-deficient rats given copper as in copper-sufficient rats. Actinomycin D blocked the stimulation of ceruloplasmin synthesis by IL-1. It was concluded that ceruloplasmin is dependent on copper incorporation for oxidase activity, but its synthesis is induced by IL-1 regardless of dietary copper levels, probably by a mechanism involving transcriptional regulation.