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Interleukin-1—Stimulated Induction of Ceruloplasmin Synthesis in Normal and Copper-Deficient Rats¹

Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611

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.

KEY WORDS: • copper • leukocytes • hormonal regulation • interleukin-1 • ceruloplasmin

¹ This research was supported by National Institutes of Health Grant No. DK 31127 from the National Institute of Diabetes, and Digestive and Kidney Diseases and by Boston Family Endowment Funds from the Institute of Food and Agricultural Sciences.

² To whom reprint requests should be addressed.

Manuscript received 18 August 1987. Revision accepted 13 November 1987.