Newberry W M, Sanford J P
J Clin Invest. 1971 Jun;50(6):1262-71. doi: 10.1172/JCI106604.
In defining host resistance factors in uremia, experiments were designed to assess the effect of renal failure serum upon the reactivity of normal human lymphocytes to phytohemagglutinin in vitro. Normal buffy coat cells were resuspended in sera obtained from normal subjects and from 14 patients with renal failure, then stimulated with phytohemagglutinin M and the cellular response measured by the increase in thymidine or uridine uptake. The mean thymidine uptake by stimulated cells in normal sera was 14,389 +/-1695 (SEM) cpm per 2 x 10(6) lymphocytes. Uridine uptake under the same conditions was 12,540 +/-1887 cpm. Compared to these are a mean thymidine uptake of 2740 +/-457 cpm and uridine uptake of 3928 +/-667 cpm in renal failure sera. Both differences are significant at P<0.01 level. For controls representing "chronic illnesses," sera from patients with pneumococcal meningitis, cirrhosis of the liver without jaundice, rheumatoid arthritis, and paraplegia with urinary tract infection did not cause suppression. No single drug had been taken by all the renal failure patients; three patients were taking no drugs. The serum from one patient with acute renal failure suppressed thymidine uptake while her serum obtained after recovery from her illness supported a normal lymphocyte response. Improvement of lymphocyte response was also noted in 9 of 10 sera obtained from patients immediately after hemodialysis. These observations plus the inhibition of stimulated cells by normal serum mixed with renal failure serum indicate the presence of a dialyzable inhibitory factor rather than the absence of a supporting factor in the renal failure sera. Lymphocytes preincubated for 24 hr in renal failure serum responded normally when transferred to normal serum and stimulated. Cells stimulated in normal serum and transferred to renal failure serum within the initial 24 hr of incubation demonstrated depressed thymidine uptake. Also, cell survival for 72 hr incubation as judged by trypan blue exclusion and chromium-51 release was similar in normal and renal failure sera. Thus, the suppressive effect of renal failure serum does not depend upon the initial phytohemagglutinin-cell interaction nor upon a significant cytotoxic effect. These studies demonstrate that a dialyzable factor(s) in the serum of patients with renal failure can greatly suppress one parameter by which an immune function of circulating lymphocytes is assessed and provides at least, a partial explanation for delayed homograft rejections in renal failure as well as the susceptibility of such patients to various infections.
在确定尿毒症患者的宿主抵抗因素时，设计了一些实验来评估肾衰竭血清对正常人淋巴细胞体外对植物血凝素反应性的影响。将正常血沉棕黄层细胞重悬于从正常受试者和14例肾衰竭患者获得的血清中，然后用植物血凝素M刺激，并通过胸苷或尿苷摄取的增加来测量细胞反应。正常血清中受刺激细胞的平均胸苷摄取量为每2×10⁶淋巴细胞14389±1695（标准误）cpm。在相同条件下尿苷摄取量为12540±1887 cpm。与之相比，肾衰竭血清中的平均胸苷摄取量为2740±457 cpm，尿苷摄取量为3928±667 cpm。两者差异均在P<0.01水平具有显著性。对于代表“慢性疾病”的对照组，肺炎球菌脑膜炎患者、无黄疸的肝硬化患者、类风湿关节炎患者以及伴有尿路感染的截瘫患者的血清均未引起抑制作用。所有肾衰竭患者均未服用单一药物；3例患者未服用任何药物。一名急性肾衰竭患者的血清抑制了胸苷摄取，而其康复后获得的血清则支持正常的淋巴细胞反应。在10例患者血液透析后立即获得的血清中，有9例也观察到淋巴细胞反应有所改善。这些观察结果加上正常血清与肾衰竭血清混合后对受刺激细胞的抑制作用表明，肾衰竭血清中存在一种可透析的抑制因子，而不是缺乏支持因子。在肾衰竭血清中预孵育24小时的淋巴细胞转移至正常血清中并受到刺激时，反应正常。在孵育的最初24小时内，在正常血清中受到刺激并转移至肾衰竭血清中的细胞，其胸苷摄取量降低。此外，通过台盼蓝排斥试验和铬-51释放试验判断，在正常血清和肾衰竭血清中孵育72小时的细胞存活率相似。因此，肾衰竭血清的抑制作用既不取决于最初的植物血凝素-细胞相互作用，也不取决于显著的细胞毒性作用。这些研究表明，肾衰竭患者血清中的一种可透析因子能够极大地抑制评估循环淋巴细胞免疫功能的一个参数，这至少为肾衰竭患者同种异体移植排斥反应延迟以及此类患者易发生各种感染提供了部分解释。
