PMID- 12846752
OWN - NLM
STAT- MEDLINE
DCOM- 20040326
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 2
DP  - 2003 Aug
TI  - Effect of iron treatment on circulating cytokine levels in ESRD patients 
      receiving recombinant human erythropoietin.
PG  - 572-8
AB  - BACKGROUND: Anemia in patients with end-stage renal disease (ESRD) is treated 
      with recombinant human erythropoietin (rhEPO) often in combination with iron. 
      However, iron catalyzes the formation of toxic radicals, which might promote 
      vascular damage, is a nutrient for microorganisms, and negatively affects immune 
      pathways, thus increasing the risk for severe infections. METHODS: We 
      investigated 28 patients on chronic hemodialysis who were randomized to receive 
      either rhEPO alone (N = 15) or rhEPO in combination with intravenous iron (N = 
      13) for a period of 12 weeks. We analyzed iron therapy associated changes in 
      cytokine patterns and endogenous radical formation. RESULTS: Tumor necrosis 
      factor-alpha (TNF-alpha) levels were increased in ESRD patients at study entry 
      and then decreased significantly over time in subjects receiving additional iron, 
      while they increased with rhEPO alone. In contrast, we found serum concentrations 
      of the anti-inflammatory cytokine interleukin (IL)-4 to increase with iron 
      therapy. A significant negative correlation between iron availability, as 
      determined by transferrin saturation, and TNF-alpha levels (P = 0.008) and a 
      positive one between transferring saturation and IL-4 (P = 0.02) pointed to the 
      potential role of iron to induce immunologic changes. Interestingly, iron therapy 
      resulted in a slight decrease in the amounts of endogenous peroxides, which may 
      be referred to reduced TNF-alpha concentrations since peroxide concentrations 
      were positively correlated to TNF-alpha levels (P = 0.046) and negatively to 
      transferrin saturation (P = 0.02). CONCLUSION: Iron supplementation in ESRD 
      patients down-regulates proinflammatory immune effector pathways and stimulates 
      the expression of the anti-inflammatory cytokine IL-4. Such a condition is 
      detrimental for host response toward invading pathogens. However, tissue damage 
      by radicals such as endogenous peroxides may be reduced in this condition due to 
      impaired TNF-alpha formation.
FAU - Weiss, Gunter
AU  - Weiss G
AD  - Department of Internal Medicine and Division of Nephrology, University Hospital 
      of Innsbruck, Innsbruck, Austria. guenter.weiss@uibk.ac.at
FAU - Meusburger, Edgar
AU  - Meusburger E
FAU - Radacher, Gudrun
AU  - Radacher G
FAU - Garimorth, Katja
AU  - Garimorth K
FAU - Neyer, Ulrich
AU  - Neyer U
FAU - Mayer, Gert
AU  - Mayer G
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11096-26-7 (Erythropoietin)
RN  - 207137-56-2 (Interleukin-4)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Aged
MH  - Anemia/*drug therapy/immunology/metabolism
MH  - Drug Therapy, Combination
MH  - Erythropoietin/*administration & dosage
MH  - Female
MH  - Humans
MH  - Interleukin-4/*metabolism
MH  - Iron/*administration & dosage
MH  - Kidney Failure, Chronic/*complications/immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Oxidative Stress
MH  - Recombinant Proteins
MH  - Renal Dialysis
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2003/07/09 05:00
MHDA- 2004/03/27 05:00
CRDT- 2003/07/09 05:00
PHST- 2003/07/09 05:00 [pubmed]
PHST- 2004/03/27 05:00 [medline]
PHST- 2003/07/09 05:00 [entrez]
AID - S0085-2538(15)49363-9 [pii]
AID - 10.1046/j.1523-1755.2003.00099.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Aug;64(2):572-8. doi: 10.1046/j.1523-1755.2003.00099.x.