Regulation of acute phase protein gene expression by ascorbic acid.

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The ODS rat, which has a hereditary defect in ascorbic acid biosynthesis, was used to investigate the effects of ascorbic acid deficiency on the hepatic gene expression of both the positive acute phase proteins, haptoglobin and alpha1-acid glycoprotein, and the negative acute phase proteins, apolipoprotein A-I and alubumin. Male ODS rats(6-week-old, body weight 140 g) were fed a diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 days. Ascorbic acid deficiency significantly elevated the serum concentration of haptoglobin and significantly lowered those of apolipoprotein A-I and albumin. The hepatic mRNA levels of haptoglobin and alpha1-acid glycoprotein in the ascorbic acid-deficient rats were significantly elevated on day 12, and reached 260% and 360% of respective values in the control rats on day 14. On the contrary, the hepatic mRNA levels of apolipoprotein A-I and albumin in the ascorbic acid-deficient rats were lowered to 68% and 71% of respective values in the control rats on day 14. Although ascorbic acid deficiency significantly elevated the serum corticosterone concentration on day 14, the changes in mRNA levels of haptoglobin, alpha1-acid glycoprotein, apolipoprotein A-I and albumin due to ascorbic acid deficiency were not affected by adrenalectomy, as assesed in a separate experiment. The serum concentration of interleukin-6, an inflammatory cytokine that stimulates gene expression of some acute phase proteins, was significantly higher in the ascorbic acid-deficient rats on day 14 than in the control rats. These results suggest that ascorbic acid deficiency causes physiologic changes similar to those that occur in the acute phase response.