Nephrol Dial Transplant (2002) 17: 39-43
© 2002 European Renal Association-European Dialysis and Transplant Association
Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines
Departments of Renal Medicine and Immunology, King's College Hospital, London, UK
Abstract
Up to 10% of patients with renal disease receiving recombinant human erythropoietin (rHuEPO) therapy show poor responsiveness to the drug. Even in patients who do respond to rHuEPO, there is a marked variability in drug sensitivity. Several factors have been recognized as causing resistance to rHuEPO, notably iron deficiency, infection/inflammation, and underdialysis. However, when these factors are excluded, the wide variation in responsiveness to rHuEPO persists. The mechanism of this effect needs to be fully elucidated. One hypothesis is that patients with uraemia showing resistance to rHuEPO may have enhanced levels of immune activation, causing increased release of pro-inflammatory cytokines in the bone marrow. Uraemia is known to be a chronic inflammatory state, with some patients showing considerably increased laboratory markers of inflammation and immune activation. Chronic inflammation can modify the process of erythropoiesis, probably mediated via pro-inflammatory cytokines such as interleukin-1 (IL-1), tumour necrosis factor-
(TNF-) and interferon-
(IFN-). The concept that rHuEPO resistance is due to enhanced levels of immune activity has been investigated by studying T-cell phenotypes using flow cytometry, as well as cytokine release from T cells and monocytes in ‘good’ and ‘poor’ responders to rHuEPO. Poor responders had significantly reduced CD28 expression on both CD4+ and CD8+ cells, enhanced IL-10 generation from peripheral blood mononuclear cells (PBMCs), higher plasma IL-12 levels, and increased TNF- and IFN- release from PBMCs. Anti-cytokine antibodies may be useful for studying inflammatory cytokine secretion from T cells in patients with renal failure. Strategies utilizing anti-cytokine therapy may prove to be a useful adjuvant in optimizing the response to rHuEPO therapy.
Keywords: anaemia; anti-cytokine therapy; chronic inflammation; drug resistance; recombinant human erythropoietin; uraemia
Notes
Correspondence and offprint requests to: Iain C. Macdougall, Consultant Nephrologist, Renal Unit, King's College Hospital, East Dulwich Grove, London SE22 8PT, UK. Email: icm\|[hyphen]\|kru{at}globalnet.co.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. S. Anand Anemia and Chronic Heart Failure: Implications and Treatment Options J. Am. Coll. Cardiol., August 12, 2008; 52(7): 501 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A Northrop-Clewes Interpreting indicators of iron status during an acute phase response - lessons from malaria and human immunodeficiency virus Ann Clin Biochem, January 1, 2008; 45(1): 18 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Toblli, A. Lombrana, P. Duarte, and F. Di Gennaro Intravenous Iron Reduces NT-Pro-Brain Natriuretic Peptide in Anemic Patients With Chronic Heart Failure and Renal Insufficiency J. Am. Coll. Cardiol., October 23, 2007; 50(17): 1657 - 1665. [Abstract] [Full Text] [PDF]
|
|