Abstract
We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VA-sufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6-treated rats compared with controls from 7.5 h throughout 7 days of infusion (P < 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days (P < 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41% lower in rhIL-6-treated rats compared with controls (P < 0.05). These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. A plausible consequence of the effect of rhIL-6-induced hyporetinolemia is that by 7 days tissues that are dependent on plasma retinol may become deprived of VA. These results have important implications in understanding the mechanism by which measles infection induces hyporetinolemia and VA deficiency of extrahepatic tissues.
Highlights
We assessed the effects of prolonged reduction of plasma retinol concentrations on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 infusion via osmotic minipumps in VAsufficient male rats
It is important to note that the reduction in plasma retinol concentrations caused by recombinant human interleukin-6 (rhIL-6) by 12 h or LPS by 24 h did not differ from each other (Ϫ42.2 Ϯ 5.4% vs. Ϫ33.5 Ϯ 16.1%, respectively; P ϭ 0.29)
The term hyporetinolemia is specific in referring to retinol, whereas hyporetinemia implies a reduction in VA including retinol, retinyl esters, and retinoic acid
Summary
We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VAsufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6-treated rats compared with controls from 7.5 h throughout 7 days of infusion (P Ͻ 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days (P Ͻ 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41% lower in rhIL-6-treated rats compared with controls (P Ͻ 0.05) These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. We hypothesize that the reduced availability of hepatic RBP can explain inflam-
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