Singh A B, Singh M, Palekar S, Levy S, Nunn C, Mann R A
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903.
J Med. 1992;23(5):289-302.
Recombinant human erythropoietin (rHuEpo) is now widely employed in correction of the anemia of end stage renal disease (ESRD). Recent reports suggest that rHUEpo, in addition to its effect on CFU-E and burst-forming-unit-erythroid (BFU-E), may stimulate granulocyte/macro-phage production and pluripotential progenitors of the myeloid and monocyte lineage. Furthermore, there is now data which demonstrate that ESRD patients who received rHuEpo have enhanced cytokine production. Taken together, these observations suggest that the administration of rHuEpo may augment the diminished immune response of renal failure patients. To evaluate the effects of rHuEpo therapy on cell-mediated immunity in hemodialysis patients, a prospective controlled study was conducted. Two parameters of immune function were tested. One was natural killer cell (NK) activity, and the other proliferation in response to the T cell mitogen concanavalin A (Con-A). NK activity of the ESRD patients was comparable with that of normal controls at the start of the study and was unaffected by rHuEpo therapy. In contrast to this, anemic ESRD patients initially demonstrated impaired mitogen driven proliferation (initial stimulation index (S.I.) = 42.5 +/- 11.9) which significantly improved following rHuEpo therapy (final S.I. = 73.3 +/- 14.7, p < 0.05). The later value exceeded the mitogen response in less anemic ESRD patients who did not receive rHuEpo (initial S.I. = 60.7 +/- 16.5, final S.I. = 61.0 +/- 16.7), but did not reach values seen in normal controls. The data suggest that rHuEpo therapy may be associated with enhanced immune responses in patients with ESRD.
重组人促红细胞生成素(rHuEpo)目前广泛应用于终末期肾病(ESRD)贫血的治疗。最近的报告表明,rHuEpo除了对红系集落形成单位(CFU-E)和爆式红系集落形成单位(BFU-E)有作用外,还可能刺激粒细胞/巨噬细胞的生成以及髓系和单核细胞系的多能祖细胞。此外,现在有数据表明,接受rHuEpo治疗的ESRD患者细胞因子生成增加。综合这些观察结果表明,给予rHuEpo可能增强肾衰竭患者减弱的免疫反应。为了评估rHuEpo治疗对血液透析患者细胞介导免疫的影响,进行了一项前瞻性对照研究。测试了两个免疫功能参数。一个是自然杀伤细胞(NK)活性,另一个是对T细胞有丝分裂原刀豆球蛋白A(Con-A)的增殖反应。在研究开始时,ESRD患者的NK活性与正常对照组相当,且不受rHuEpo治疗的影响。与此相反,贫血的ESRD患者最初表现出有丝分裂原驱动的增殖受损(初始刺激指数(S.I.)= 42.5 +/- 11.9),rHuEpo治疗后显著改善(最终S.I. = 73.3 +/- 14.7,p < 0.05)。后期的值超过了未接受rHuEpo治疗的轻度贫血ESRD患者的有丝分裂原反应(初始S.I. = 60.7 +/- 16.5,最终S.I. = 61.0 +/- 16.7),但未达到正常对照组的值。数据表明,rHuEpo治疗可能与ESRD患者免疫反应增强有关。