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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
Author(s) -
Richard A Feelders,
Gerard Vreugdenhil,
A. M. M. Eggermont,
P.A. Kuiper-Kramer,
H.G. Van Eijk,
A. J. G. Swaak
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00323.x
Subject(s) - transferrin , ferritin , transferrin receptor , tumor necrosis factor alpha , receptor , cancer , interferon , medicine , metabolism , endocrinology , necrosis , acute phase protein , immunology , cancer research , chemistry , inflammation
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 (rIFN‐γ) 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 4 h to peak levels at day 2, whereas α 1 ‐antitrypsin and α 1 ‐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 IFN‐γ.