title: Inflammation, T-cell phenotype, and inflammatory cytokines in chronic kidney disease patients under hemodialysis and its relationship to resistance to recombinant human erythropoietin therapy.
abstract: BACKGROUND
  Resistance to recombinant human erythropoietin (rhEPO) occurs in some chronic kidney disease (CKD) patients, which may be due to enhanced systemic inflammatory response and to the erythropoiesis-suppressing effect of pro-inflammatory cytokines, some of which are produced by T cells.
  
  
  OBJECTIVE
  The aim of this study was to investigate the relationship between resistance to rhEPO therapy in hemodialysis CKD patients and inflammatory markers [C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (sIL2R), and serum albumin levels], blood cell counts, T-cell phenotype, cytokine production by T cells, and serum cytokine levels.
  
  
  METHODS
  We studied 50 hemodialysis CKD patients, 25 responders and 25 nonresponders to rhEPO, and compared them to each other and with 25 healthy controls. When compared to controls, CKD patients showed increased serum levels of CRP, IL-6, and sIL2R and a T-cell lymphopenia, due to decreased numbers of both CD4+ and CD8+ T cells. T cells from CKD patients had an immunophenotype compatible with chronic T-cell stimulation as shown by the increased percentage of CD28-, CD57+, HLA-DR+, CD28-HLA-DR+, and CD57+ HLA-DR+ T cells and produce higher levels of IL-2, INF-gamma, and TNF-alpha after short-term in vitro stimulation, although Th1 cytokines were not detectable in serum. Statistically significant differences were found between responders and nonresponders to rhEPO therapy for total lymphocyte and CD4+ T-lymphocyte counts, albumin (lower in nonresponders) and CRP (higher in nonresponders) levels.
  
  
  CONCLUSIONS
  CKD patients under hemodialysis present with raised inflammatory markers and decrease of total lymphocyte and CD4+ T-lymphocyte counts when compared with controls. Some of those markers are even further enhanced in nonresponders to rhEPO therapy patients, but resistance to this therapy cannot be justified by a Th1 polarized T-cell response.
authors.affiliation: Serviço de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Rua Anibal Cunha, 164, 4099-030 Porto, Portugal. elisio.costa@ipb.pt
authors.forename: Elísio
authors.initials: E
authors.lastname: Costa
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.forename: João Moura
authors.initials: JM
authors.lastname: Alves
authors.forename: Susana
authors.initials: S
authors.lastname: Rocha
authors.forename: Petronila
authors.initials: P
authors.lastname: Rocha-Pereira
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Castro
authors.forename: Vasco
authors.initials: V
authors.lastname: Miranda
authors.forename: Sameiro Faria Maria
authors.initials: SF
authors.lastname: do
authors.forename: Alfredo
authors.initials: A
authors.lastname: Loureiro
authors.forename: Alexandre
authors.initials: A
authors.lastname: Quintanilha
authors.forename: Luís
authors.initials: L
authors.lastname: Belo
authors.forename: Alice
authors.initials: A
authors.lastname: Santos-Silva
mesh_terms: D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D004351:Drug Resistance / Q000276:immunology*; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D004921:Erythropoietin