Regulation of iron metabolism in the acute-phase response: Interferon γ and tumour necrosis factor α induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients

R. A. Feelders, G. Vreugdenhil, A. M.M. Eggermont, P. A. Kuiper-Kramer, H. G. Van Eijk, A. J.G. Swaak

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Background - The acute-phase response and anaemia of chronic disease are characterized by hypoferraemia associated with an increased ferritin synthesis, which might be mediated by the activated cytokine cascade. Methods - We examined the prolonged effects of isolated limb perfusion (ILP) with recombinant human tumour necrosis factor α (rTNF), recombinant human interferon γ (rIFNγ) and melphalan on interleukin (IL) 6 and acute-phase protein levels, iron status and serum transferrin receptor (sTfR) levels in 12 patients with melanoma or sarcoma. Patients were treated with ILP during 90 min after pretreatment with rIFN-γ during 2 days. Results - After ILP, leakage of TNF resulted in systemic peak levels at 3 min followed by an increase in IL-6 with maximum levels at 4 h. C-reactive protein (CRP) rose at 4h to peak levels at day 2, whereas α1-antitrypsin and α1-acid glycoprotein increased to maximum levels at day 3. Albumin and transferrin levels decreased after ILP and recovered after day 2. Serum iron and sTfR levels decreased during pretreatment and after ILP to minimum levels at 8 h and day 1 respectively. This was associated with an increase in serum ferritin levels, which paralleled CRP values. Conclusions - Our data point to a central role for the cytokine network in the modulation of iron metabolism in the acute-phase response and anaemia of chronic disease. TNF, possibly via induction of IL-6, and IFN-γ induce hypoferraemia, which may in part result from a decrease in tissue iron release based on a primary stimulation of ferritin synthesis. The fall in sTfR levels may reflect an impaired erythroid growth and/or TfR expression mediated by TNF and IFNγ.

Originele taal-2Engels
Pagina's (van-tot)520-527
Aantal pagina's8
TijdschriftEuropean Journal of Clinical Investigation
Volume28
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - 1998
Extern gepubliceerdJa

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