Impact of iron treatment on immune effector function and cellular iron status of circulating monocytes in dialysis patients.
BACKGROUND
Iron is used as an adjunct therapy to treat anaemia in dialysis patients. However, iron may harbour detrimental effects in being a nutrient for invading pathogens or by modulating immune pathways. Thus, we prospectively studied the effects of iron treatment towards monocyte immune function.


METHODS
Twenty-four haemodialysis patients in whom iron therapy was withheld for 2 weeks before study entry were randomly assigned to receive either a single parenteral dose of iron sucrose or saline (control), and the effects on iron status and immune function of patients' monocytes were analysed during follow-up.


RESULTS
At baseline, we found an inverse relationship between serum ferritin levels and the inducibility of patients' monocytes for interleukin-6 and tumour necrosis factor-alpha formation following ex vivo immune stimulation. However, 48 h after intravenous iron administration, we observed a transient increase of tumour necrosis factor-alpha and interleukin-6 formation by unstimulated monocytes as compared with control subjects. This could be traced back to increased phosphorylation of nuclear factor kappa-B p65 in monocytes following iron treatment, which was more pronounced when pre-treatment serum ferritin levels were low. In parallel, intravenous iron injection resulted in storage of the metal in circulating monocytes as reflected by an increase of intracellular ferritin levels, and the amount of iron retention was positively associated with circulating concentrations of the iron regulatory peptide hepcidin.


CONCLUSIONS
Intravenously administered iron is taken up by monocytes and leads to short-term activation of the nuclear factor kappa-B pathway. However, increased circulating ferritin levels are associated with an impaired immune response of monocytes. In addition, circulating hepcidin concentrations may determine the erythropoietic response to iron injection by modifying iron retention within monocytes.
Sonnweber
Thomas
T
Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Medical University of Innsbruck, Innsbruck, Austria.
Theurl
Igor
I
Seifert
Markus
M
Schroll
Andrea
A
Eder
Susanne
S
Mayer
Gert
G
Weiss
Günter
G
D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005293:Ferritins / Q000097:blood*; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D019266:Iron, Dietary / Q000378:metabolism* / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000098742:Ferroportin
D015703:Antigens, CD; D023181:Antimicrobial Cationic Peptides; C068126:CD71 antigen; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D019266:Iron, Dietary; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin; D005293:Ferritins