Immunomodulatory action of human recombinant erythropoietin in man

Erythropoietin exerts direct immunomodulatory effects on the cytokine production by activated human T-lymphocytes

“…Data obtained in this study showed that Epo was incapable of furnishing significant direct influence on T cell activation status, as judged from СD38 and СD25 cell surface expression levels. We speculate therefore that that suppressive Epo-mediated effects on T cell blastogenesis described previously [9] may be of an indirect nature.…”

“…On the other hand, there is evidence to suggest that Epo possesses intrinsic immunosuppressive activity. Thus, Epo was shown to suppress mitogen-induced lymphocyte proliferation [9], and ameliorate the development of experimental autoimmune encephalomyelitis (EAE) in mice [10]. This particular clinical effect of Epo is ascribed to its ability to down-regulate the activity of a transcription nuclear factor kappalight-chain-enhancer of activated B cells (NF-κB) and NF-κB-dependent production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-6 и IL-17 [10].…”

Patch-Clamp Study on T-Lymphocyte Potassium Conductance in Patients with Chronic Renal Failure

“…Wheth er this effect is caused by direct rHuEPO interaction with its putative receptors on TL cell membrane or with relat ed IL-2 receptors, remains to be clarified [27,30], What ever the mechanism of action of rHuEPO on TL is, the way of involvement of the potassium channels in this pro cess remains to be elucidated. In particular, it would be interesting to correlate the observed decrease in gK* values induced by treatment with rHuEPO and the modulation of TL function by this substance.…”

“…EPO that we noticed to significantly decrease the TL gK* value in the uremic patients, was found to exert an immunomodulatory effect in uremic patients [27], proba bly due to a direct action of rHuEPO on TL [28][29][30], It has been demonstrated that rHuEPO treatment causes a decrease of expression of DR+ antigens on T cells. Wheth er this effect is caused by direct rHuEPO interaction with its putative receptors on TL cell membrane or with relat ed IL-2 receptors, remains to be clarified [27,30], What ever the mechanism of action of rHuEPO on TL is, the way of involvement of the potassium channels in this pro cess remains to be elucidated.…”

Prospective Study of the Immune Effects of Normalizing the Hemoglobin Concentration in Hemodialysis Patients Who Receive Recombinant Human Erythropoietin

“…In vitro cytokine production of interleukin-2, ␥-IFN, colony-stimulating factor, and TNF were found by Gafter et al (17) to increase progressively and in parallel to the rise in hemoglobin levels achieved by rHuEPO or RBC transfusions in ESRD patients or after autologous transfusions in normal subjects. In vitro T-lymphocyte proliferation to monoclonal antibody to CD3 antigen (OKT3) and alloantigen (HLA-D) was enhanced by high-dose rHuEPO incorporated into media (11). Addition of rHuEPO, alone, to the media did not stimulate lymphocyte proliferation.…”