Short-Term Effect of Erythropoietin on T-Cell Mitogenic Proliferation in Chronic Renal Failure Patients

Shurtz-Swirski, Revital; Kristal, Batia; Shkolnik, Tamar; Weissman, Irit; Shapiro, Galina; Shasha, Shaul M.

doi:10.1159/000188802

Cited by 17 publications

(13 citation statements)

References 6 publications

(6 reference statements)

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“…Previous reports, mostly regarding dialysis patients, have implied that Epo treatment is associated with improved immunological functions [19,20,36,37]. rHuEpo therapy in these patients was associated with repair of T cell functions [36,38], probably via indirect mechanisms [39], as well as normalization of proinflammatory and anti-inflammatory cytokine levels [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…rHuEpo therapy in these patients was associated with repair of T cell functions [36,38], probably via indirect mechanisms [39], as well as normalization of proinflammatory and anti-inflammatory cytokine levels [40,41]. The discrepancies in data on dialysis patients, showing in some cases increased antibody response to an administered antigen [19,24], and in others no statistically significant difference in the level of antibodies detected [25] deserve proper attention.…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrated that higher levels of endogenous Ig j light chains in the Epo-treated mice, prior to the time of appearance of the pathological paraprotein [32], was associated with improved survival. This Epomediated enhancement of the normal Ig is of particular importance in a disease characterized by bone marrow dysfunction, caused by excessive plasma cell proliferation and secretion of the pathological protein.Previous reports, mostly regarding dialysis patients, have implied that Epo treatment is associated with improved immunological functions [19,20,36,37]. rHuEpo therapy in these patients was associated with repair of T cell functions [36,38], probably via indirect mechanisms [39], as well as normalization of proinflammatory and anti-inflammatory cytokine levels [40,41].…”

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Erythropoietin enhances immune responses in mice

et al. 2007

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Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an antineoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8 + T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.See accompanying commentary: http://dx.doi. org/10.1002/eji.200737401 Introduction Erythropoietin (Epo), produced mainly in the adult kidney, is the major growth regulator of the erythroid cell lineage. Cloning of the Epo gene has led to the introduction of recombinant human Epo (rHuEpo) into clinical practice as a treatment for various anemias, including anemia related to chronic kidney disease and certain forms of cancer [1, 2]. Detection of the target receptor for Epo (EpoR) in cells other than erythroid progenitors, such as polymorphonuclear leukocytes, megakaryocytes, endothelial, myocardial and neural cells [3][4][5][6][7], suggests that Epo has other biological functions beyond erythropoiesis, and may have further potential therapeutic applications. These effects include improvement in congestive heart failure [8,9] and neuroprotection [10][11][12][13][14][15][16][17].* These authors contributed equally to this study. The idea that rHuEpo may have an important effect on the immune system, including both cellular and humoral type responses, derives from several lines of data, as recently reviewed [18]. For instance, clinical observations revealed that treatment with rHuEpo was associated with enhanced antibody production in hemodialysis patients, demonstrated for T cell-dependent antigens, such as tetanus toxoid and hepatitis B [19][20][21][22] as well as for the T cell-independent pneumococcal polysaccharide antigen [20]. Others have demonstrated enhancement of basal and mitogen-stimulated immunoglobulin production by cultured peripheral mononuclear cells (MNC) of dialysis patients treated ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Erythropoietin enhances immune responses in mice

et al. 2007

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“…For example, several investigators demonstrated that EPO treatment causes an increase in the peripheral thrombocyte count and an improvement in the hemostatic defect of uremia in HD patients [3, 4]. We have previously shown that EPO improves T cell mitogenic proliferation [5]. EPO can influence granulocytic-monocytic progenitor growth and numbers, but the data are conflicting, as some investigators have reported an increase in numbers [6], whereas others reported no change or a decrease [7, 8, 9, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

Interaction between Erythropoietin and Peripheral Polymorphonuclear Leukocytes in Hemodialysis Patients

Kristal

Shurtz-Swirski²,

Shasha

et al. 1999

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The effect of erythropoietin (EPO) on the oxidative stress and inflammation caused by polymorphonuclear leukocytes (PMNLs) in chronic hemodialysis (HD) patients was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of healthy controls and HD patients before and following 6 weeks of EPO treatment. The oxidative stress was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate stimulated PMNLs, and the inflammatory state was evaluated by in vitro PMNL survival, in addition to white blood cell and PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment, in HD patients, the rate of superoxide release from PMNLs as well as WBC and PMNL counts fell significantly when compared with the pretreatment values. PMNLs from HD patients and healthy controls incubated in vitro with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release and a significant improvement in survival. We have concluded that EPO interacts with PMNLs, attenuating their primed state in HD patients, thus reducing oxidative stress and the extent of inflammation. To the best of our knowledge, this attenuation of the primed state of PMNLs by EPO is a new finding.

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“…This suggests that better cutaneous reactivity is not related to the upregulation of IL-2 or OKT3 receptors or increase in cytokine levels. A previous study (12) showed better lymphocyte mitogenic response to OKT3 in dialysis patients with partially corrected anemia using rHuEPO. In our study, CD8 counts were significantly higher in the anemic group over time.…”

Section: Discussionmentioning

confidence: 85%