The "acute phase" is clinically characterized by homeostatic alterations such as
somnolence, adinamia,
fever,
muscular weakness, and
leukocytosis. Dramatic changes in
iron metabolism are observed under acute-phase conditions. Rats were administered
turpentine oil (TO) intramuscularly to induce a sterile
abscess and killed at various time points. Tissue
iron content in the liver and brain increased progressively after TO administration. Immunohistology revealed an abundant expression of
transferrin receptor-1 (TfR1) in the membrane and cytoplasm of the liver cells, in contrast to almost only nuclear expression of TfR1 in brain tissue. The expression of TfR1 increased at the
protein and
RNA levels in both organs. Gene expression of
hepcidin,
ferritin-H,
iron-regulatory protein-1, and
heme oxygenase-1 was also upregulated, whereas that of hemojuvelin, ferroportin-1, and the
hemochromatosis gene was significantly downregulated at the same time points in both the brain and the liver at the
RNA level. However, in contrast to observations in the liver, gene expression of the main acute-phase
cytokine (interleukin-6) in the brain was significantly upregulated. In vitro experiments revealed TfR1 membranous
protein expression in the liver cells, whereas nuclear and cytoplasmic TfR1
protein was detectable in brain cells. During the non-bacterial acute phase,
iron content in the liver and brain increased together with the expression of TfR1. The
iron metabolism
proteins were regulated in a way similar to that observed in the liver, possibly by locally produced acute-phase
cytokines. The significance of the presence of TfR1 in the nucleus of the brain cells has to be clarified.