Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats.
To explore a mechanism of interleukin (IL)-6-induced hypoferremia in rats, iron metabolism was investigated both in vivo and in vitro. Recombinant IL-6 was intraperitoneally administered to male Wistar rats and the serial change of parameters related to iron metabolism was examined. After administration of IL-6, plasma IL-6 concentration increased rapidly, reached its maximum in 1 hr and thereafter decreased quickly. Plasma IL-6 3 hr after IL-6 injection (50 micrograms/kg) was 3 units/ml, which is a concentration capable of inducing hepatic 125I-labeled transferrin uptake in vitro using isolated hepatocytes. Plasma iron concentration and transferrin saturation had decreased to approximately one third of the initial level within 3 hr and then recovered. Total iron binding capacity remained unchanged for 6 hr, then began to decrease. Red blood cell count and hemoglobin concentration showed no remarkable changes during this period. By ferrokinetic study with plasma that contained iron 59-labeled transferrin, the plasma iron disappearance half time, calculated from the disappearance curve, was significantly shortened from 55 min to 22 min by IL-6 treatment (p < 0.01). The ferritin concentration in the liver was increased significantly after the administration of IL-6 (p < 0.001), but transiently decreased in the spleen. The plasma ferritin showed a gradual increase during the 6-hr period after IL-6 injection. The uptake of 125I-labeled diferric transferrin by isolated hepatocytes was increased by IL-6 treatment and this increment was inhibited by addition of 100-fold excess unlabeled transferrin. On the other hand, no significant increment of 125I-labeled diferric transferrin uptake was observed in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Kobune
M
M
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Kohgo
Y
Y
Kato
J
J
Miyazaki
E
E
Niitsu
Y
Y
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count / Q000187:drug effects; D005293:Ferritins / Q000096:biosynthesis*; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007501:Iron / Q000097:blood / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D014168:Transferrin / Q000493:pharmacokinetics*
D006454:Hemoglobins; D015850:Interleukin-6; D011994:Recombinant Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron