ANEMIA OF UREMIA IS ASSOCIATED WITH REDUCED IN-VITRO CYTOKINE SECRETION - IMMUNOPOTENTIATING ACTIVITY OF RED-BLOOD-CELLS

Many in vitro studies demonstrate various stimulatory effects of red b lood cells (RBC) on T cell reactivity. Only a few suggest a role for R BC in vivo, such as decreased B and T cell function in iron deficiency anemia. Immune deficiency of uremia is only partially corrected by di alysis treatment. We postulated therefore that this anemia may contrib ute in part to the immune deficiency of uremia. The aim of our study w as to evaluate this postulate and to investigate the role RBC may have in the immune system in vivo. The in vitro secretion of interleukin-2 (IL-2), gamma-interferon (gamma-IFN), tumor necrosis factor (TNF) and colony stimulating factor (CSF) by human peripheral blood mononuclear cells isolated from patients and controls was used as a measure of im mune function. The following protocols were carried out: IL-2 secretio n was measured in patients with end-stage renal disease (ESRD) and in controls. RBCs were transfused to patients with ESRD and secretion of cytokines was measured before, and 4 hours, 4, 7 and 14 days afterward s; patients with ESRD received recombinant human erythropoietin (rHuEp o) and secretion of cytokines was measured before treatment and two an d four months later. Finally, the effect of phlebotomy and transfusion of the autologous blood on cytokine secretion in healthy subjects was measured. Secretion of IL-2 by patients with ESRD was substantially l ower than that of healthy subjects. In each group, IL-2 secretion corr elated positively with hemoglobin level, r = 0.73, P < 0.01 and r = 0. 71, P < 0.01. Following transfusion of RBC, secretion of all cytokines rose at the early stage of the study and stayed elevated throughout t he study period. Following treatment with rHuEpo secretion of the four cytokines rose progressively and in parallel to the rise in hemoglobi n level as shown by a positive correlation between each of the cytokin es and the hemoglobin level. Phlebotomy caused a significant reduction in the secretion of the four measured cytokines. Transfusion of autol ogous blood led to a significant rise in cytokine secretion above prep hlebotomy levels which persisted throughout the study. These results s uggest that the anemia of uremia may be associated with a decreased se cretion of cytokines in vitro. This could contribute to the impaired i mmune response observed in patients with ESRD. Furthermore, RBC appear to potentiate secretion of cytokines. The decreased secretion of cyto kines may be corrected in part by RBC transfusion or elevation of hemo globin levels with rHuEpo treatment.