Abstract
Recombinant human erythropoietin (rhEPO) treatment of hemodialyzed (HD) patients normalizes the altered phenotype of CD4+ lymphocytes and restores the balance of Th1/Th2 cytokines. We decided to test how the presence of rhEPO in cell culture modulates cytokine production of CD4+ lymphocytes in HD patients with stable hemoglobin level and expression of activation antigens of stimulated CD4+ lymphocytes similar to those observed in healthy individuals. We also tested whether the presence of rhEPO in cell culture protects stimulated CD4+ lymphocytes of HD patients from apoptosis. Peripheral blood mononuclear cells (PBMC) of HD patients were stimulated with an immobilized anti-CD3 antibody with or without addition of rhEPO. The percentage of apoptotic CD4+ lymphocytes and the level of Th1/Th2 cytokines in culture supernatants were measured with flow cytometry. HD patients showed a decrease in the percentage of apoptotic CD4+ cells after stimulation with the anti-CD3 antibody combined with rhEPO. The level of IFN-γ and IL-10 was increased while the level of TNF-α was decreased in the presence of rhEPO in cell culture from HD patients. These results confirm the role of rhEPO signaling in T lymphocytes of HD patients.
Highlights
Chronic renal failure is accompanied by a deficiency state in both cell-mediated and humoral immunity which is deepened by hemodialysis (HD) [1]
We have recently shown that Recombinant human erythropoietin (rhEPO) increases the phosphorylation of signal transducer and activator of transcription 5 (STAT5) in stimulated CD4+ lymphocytes [12]
We examined whether the presence of rhEPO in cell culture can protect stimulated CD4+ lymphocytes of HD patients from apoptosis and we have shown that if present at a concentration similar to the physiological level rhEPO promotes the survival of CD4+ lymphocytes
Summary
Chronic renal failure is accompanied by a deficiency state in both cell-mediated and humoral immunity which is deepened by hemodialysis (HD) [1]. The deficient production of cytokines is probably related to changes in phenotype of CD4+ lymphocytes from HD patients, which exhibit decreased expression of the major co-stimulatory CD28 antigen and main activation markers: CD25 and CD69 [6]. The level of TNF-α and IL-10 changes immediately when the hemoglobin level exceeds the optimal value of 10 g/dl and is stable during treatment, while the level of IL-2 increases continuously during treatment [9]. This observation suggests that the normalization of the levels of TNF-α and IL10 was reached shortly after the start of rhEPO therapy. Increase of the level of IL-2 has been achieved after several months of rhEPO administration, so
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