TY - JOUR
T1 - Regulation of iron metabolism in the acute-phase response
T2 - Interferon γ and tumour necrosis factor α induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients
AU - Feelders, R. A.
AU - Vreugdenhil, G.
AU - Eggermont, A. M.M.
AU - Kuiper-Kramer, P. A.
AU - Van Eijk, H. G.
AU - Swaak, A. J.G.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - Acute-phase response
KW - Anaemia of chronic disease
KW - Cytokines
KW - Ferritin
KW - Hypoferraemia
KW - Serum transferrin receptor
UR - http://www.scopus.com/inward/record.url?scp=0031857792&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2362.1998.00323.x
DO - 10.1046/j.1365-2362.1998.00323.x
M3 - Article
C2 - 9726030
AN - SCOPUS:0031857792
SN - 0014-2972
VL - 28
SP - 520
EP - 527
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
IS - 7
ER -