混合培养的供、受者骨髓细胞过继回输延长小鼠移植心脏存活时间

目的 将供、受者骨髓细胞经混合培养后过继回输,以观察其对同种异体移植心脏存活时间和受者免疫功能的影响.方法 取Balb/c小鼠和C57BL/6J小鼠的骨髓细胞,进行混合培养.配制含Balb/c小鼠和C57BL/6J小鼠脾淋巴细胞的混合淋巴细胞反应体系(MLR)以及含Balb/c小鼠和C3H小鼠脾淋巴细胞的MLR,分别加入混合培养的骨髓细胞,观察其对MLR中细胞增殖的影响.以C57BL/6J小鼠为供者,Balb/c小鼠为受者行腹腔异位心脏移植,实验分为4组:(1)移植对照组,受者仅进行心脏移植,不作其他处理;(2)实验对照组,心脏移植后给予西罗莫司灌胃;(3)实验组,移植手术结束前注射混合培养的骨髓细胞1×10~7个,术后给予西罗莫司;(4)第三方对照组,受者接受C3H小鼠的移植心脏,手术结束前注射混合培养的骨髓细胞1×10~7个,术后给予西罗莫司.记录移植心脏存活时间;移植心脏停跳当日,取受者外周血,检测CD4~+ CD25~+ T淋巴细胞的比例及供者来源的H-2K~b细胞的比例.结果 加入混合培养的骨髓细胞后,Balb/c和C57BL/6J的MLR的淋巴细胞增殖率低于Balb/c和C3H的MLR.实验组移植心脏的存活时间长于其他3组(P<0.05).实验组CD4~+CD25~+T淋巴细胞的百分率高于其他3组(P<0.05).实验组外周血中H-2K~b细胞的比例高于其他3组(P<0.05).结论 受者输注混合培养的供、受者骨髓细胞可在一定程度上调节免疫应答,延长小鼠移植心脏的存活时间,该作用具有供者抗原特异性.     

ICOS-Ig 融合蛋白联合亚剂量环孢素A诱导小鼠移植心脏长期存活

目的 探讨可诱导共刺激分子-Ig融合蛋白(ICOS-Ig)联合亚剂量环孢素A(CsA)对小鼠移植心脏存活时间的影响及其机制.方法 自行构建ICOS-Ig.以Balb/c小鼠为供者,C57BL/6小鼠为受者,套管法制备小鼠颈部心脏移植模型,然后将模型分为5组:(1)未处理组,不做任何处理;(2)对照IgG组,移植当天以及术后第2、4、6天腹腔注射IgG 250 μg;(3)IcoS-Ig组,移植当天以及术后第2、4、6天腹腔注ICOSIg250 μg;(4)CsA组,移植当天以及术后第1～7天腹腔注射CsA 10mg/kg;(5)ICOS-Ig+CsA组,同时给予ICOS-Ig和CsA,使用时间和剂量同前.术后观察移植心脏存活时间,观察移植后第7天移植心脏的病理变化,并进行供、受者混合淋巴细胞反应(MLR),测定受者血清中供者特异性的同种抗体水平.结果 各组小鼠移植心脏存活时间分别为:未处理组(8.5±1.5)d,对照IgG(8.00.8)d,ICOSIg(29.57.7)d.CsA处理组(21.0±5.0)d,ICOS-Ig+CsA组移植心脏存活时间均超过50d,6只(6/9)移植心脏存活时间>100d,ICOS-Ig+CsA组与其他4组比较,差异均有统计学意义(P<0.01).移植后7d,未处理组及对照IgG组心肌明显变性,纤维断裂,间质水肿,肌束间及血管周围有大量炎症细胞浸润,而ICOS-Ig组和CsA组心肌无明显变性,间质略水肿,血管周围有少量淋巴细胞浸润,ICOS-Ig+CsA组的病理改变明显I(X)S-Ig组和CsA组.移植后7d,ICOS-Ig组和CsA组的脾脏淋巴细胞对同种抗原刺激反应比未处理组和对照IgG组明显降低(P<0.05),而ICOS-Ig+CsA组的抑制作用明显强于ICOS-Ig组和CsA组(P<0.05).移植后7d,ICOS-Ig组和CsA组受者血清中针对特异性供者的抗体水平明显低于未处理组和对照IgG组(P<0.05),ICOS-Ig+CsA组的抗体水平明显低于ICOS-Ig组和CsA组(P<0.05).结论 ICOS-Ig可以降低受者对供免疫反应性,延长移植心脏的存活时间,联合亚剂量CsA可使异体移植心脏长期存活.     

1,25-(OH)2D3对小鼠皮肤移植后脾T细胞亚群、MLR及NK细胞活性的影响

目的探讨1,25-二羟维生素D3[1,25-(OH)2D3]抑制机体免疫功能的机理,为用于临床抗排斥治疗提供实验依据.方法建立不同系小鼠间皮肤移植的动物模型.术日将实验小鼠随机分为四组,均用小鼠灌胃器给药.对照组:每日20ml/kg生理盐水; 维生素D3(VD3)组:单独应用1,25-(OH)2D3 2.5μg*kg-1*d-1; 环孢素A(CsA)组:单独应用CsA 25mg*kg-1*d-1; VD3+CsA组:联合应用VD3+CsA,按VD3组和CsA组用药剂量给药.术后10d,测定小鼠脾的T细胞亚群、单向混合淋巴细胞反应(MLR)、自然杀伤细胞(NK)活性.结果 VD3组的移植皮片存活时间(13.13±1.13)d,明显长于对照组的(9.75±0.89)d;CD3+、CD4+ T细胞百分率40.19%±4.25%、24.65%±3.47%均明显低于对照组48.70%±7.19%、 33.55%±4.34%,P<0.01;对BALB/C鼠的MLR(0.95±0.12)明显低于对照组(1.19±0.22),P<0.05; NK细胞的活性与对照组小鼠比较, 差异无显著性.结论 1,25-(OH)2D3能延长小鼠皮肤移植的存活时间,其抑制机体免疫功能的作用是通过减少CD3+、CD4+ T细胞的数量及抑制T细胞功能而发挥的,对NK细胞活性无明显影响.     

体内注射白细胞介素10和转化生长因子质粒延长小鼠移植皮肤存活时间

目的 探讨体内注射白细胞介素10(IL-10)和转化生长因子β1(TGF-β1)质粒对小鼠移植皮肤存活时间的影响.方法 构建含IL-10和TGF-β1基因的质粒,以Balb/c小鼠为受者、Balb/c小鼠与C57BL/6小鼠杂交的F1代小鼠为供者,行皮片移植.移植当天,经尾静脉分别给受者快速注射不含基因的空白质粒(空白组)、含IL-10基因质粒(IL-10组)、含TGF-β1基因质粒(TGF-β1组)以及含IL-10和TGF-β1双基因的质粒(联合组),以后每2天注射1次,20 μg/次,共注射6次,观察移植皮肤存活时间.另取Balb/c小鼠,在输注C57BL/6小鼠脾细胞后,按前述分组及方法接受质粒快速注射,注射5次后,分离其脾细胞,以流式细胞仪检测脾细胞中CD4+ CD25+ T淋巴细胞含量.结果 移植皮片存活时间,空白组为(13.50±1.04)d,IL-10组为(13.83±1.16)d,TGF-β1组为(15.33±1.50)d,联合组为(21.33±3.20)d,联合组移植皮片存活时间明显长于其他3组(P<0.01).脾细胞中CD4+ CD25+ T淋巴细胞的含量,空白组为(6.58±1.86)%,IL-10组为(10.52±1.13)%,TGF-β1组为(14.44±0.42)%,联合组为(14.25±1.24)%,TGF-β1组和联合组的CD4+ CD25+ T淋巴细胞含量明显高于空白组和IL-10组(P<0.01).结论 体内注射IL-10和TGF-β1质粒可延长小鼠移植皮肤存活时间,并能提高CD4+ CD25+ T淋巴细胞含量.     

T细胞疫苗诱导大鼠同种异体肢体移植免疫耐受的实验研究

目的 探讨T细胞疫苗（TCV）诱导大鼠同种异体肢体移植特异性免疫耐受的作用。方法 制备受者Lewis大鼠针对供者DA大鼠的TCV，应用TCV，免疫正常Lewis大鼠共3次，每周1次。设TCV组和TCV未接种组，在接种前及接种后5d进行混合淋巴细胞培养（MLR）；设TCV组、CsA组和空白对照组，于接种后7d进行DA大鼠针对Lewis大鼠的同种异体肢体移植，在术后7d进行淋巴细胞毒检测，术后21d进行嵌合分析。结果 MLR显示，Lewis大鼠的脾细胞反应程度接种组显著低于未接种组（P〈0．01）；微量细胞毒测定显示，死亡细胞百分率在TCV组、CsA组、空白对照组3组比较性差异有统计学意义（P〈0．01）；嵌合分析显示经处理的Lewis大鼠脾脏，胸腺中检测出了DA大鼠源性的骨髓嵌合体。结论 T细胞疫苗可以抑制受者对供者的免疫应答；作为骨髓移植前预处理手段，T细胞疫苗接种后行吻合血管的骨髓移植成功地诱导出同种异体肢体移植嵌合耐受。     

异基因小鼠髓腔内骨髓移植诱导免疫耐受

目的探讨异基因小鼠髓腔内骨髓移植(IBM-BMT)诱导免疫耐受的效果。方法雄性BALB/c小鼠和雌性C57BL/6小鼠分别作为骨髓移植的供、受者。受者预处理后进行IBM-BMT,建立异基因小鼠骨髓移植模型。通过皮肤移植和混合淋巴细胞反应(MLR)对受者的耐受状态进行检测。结果接受过IBM-BMT的受者进行供者来源的皮肤移植,移植物的存活时间>300d,较对照组的(12.7±1.63)d明显延长(P<0.01),而受者接受来自无关供者(KM小鼠)的皮肤移植物存活时间未见延长。接受过IBM-BMT的受者脾细胞对供者脾细胞的MLR增殖率均明显降低,与对照组比较,P<0.01,而对无关供者的脾细胞仍表现强烈的增殖反应。结论应用IBM-BMT可以诱导受者获得供者抗原的特异性免疫耐受,使移植物存活时间延长。     

伊马替尼联合供者淋巴细胞输注治疗造血干细胞移植后慢性粒细胞白血病复发

目的 探讨伊马替尼联合供者淋巴细胞输注(DLI)治疗异基因造血干细胞移植后慢性粒细胞白血病(CML)复发的效果.方法 3例CML(慢性期)患者,在接受预处理后,例1接受其胞妹外周血造血干细胞移植,例2接受其胞兄的骨髓移植,例3接受其胞弟的骨髓与外周血造血干细胞联合移植.例1移植后采用环孢素A(CsA)和霉酚酸酯(MMF)预防移植物抗宿主病(GVHD),例2采用CsA、短程甲氨蝶呤(MTX)、抗胸腺细胞球蛋白及抗CD25单克隆抗体预防GVHD,例3应用CsA、MTX和MMF预防GVHD.采用细胞遗传学及荧光原位杂交技术动态监测治疗效果.移植后发生血液学复发时,给予伊马替尼口服,并行DLI.结果 例1移植后30 d行DLI,输注CD3+T淋巴细胞0.5×107 /kg,移植后50 d和70 d,再次行DLI,分别输注CD3+ T淋巴细胞1.0 × 107 /kg和2.0×107 /kg,短串联重复序列(STR)检测提示为完全供者嵌合(DC).移植后120 d,疾病进展,给予伊马替尼400 mg/d,同时输注供者CD3+ T淋巴细胞2.5 × 107/kg.移植后180 d,STR检查提示仍为DC.患者最终于移植后17个月因髓外复发死亡.例2的染色体核型于移植后35 d转变为46,XY,XY为100%,BCR-ABL融合基因阴性.移植后100 d,原发病复发.停用免疫抑制剂,输入供者CD3+ T淋巴细胞3.9×107 /kg,同时口服伊马替尼500 mg/d.DLI联合伊马替尼治疗后30 d,患者的染色体核型为46,XY,XY为100%,BCR-ABL融合基因阴性,患者至今无病存活53个月.例3移植后5 d造血功能获得重建,移植后60 d,染色体核型为46,XY.移植后120 d,确诊CML复发,遂给予伊马替尼400 mg/d,并行DLI,共输注供者CD3+ T淋巴细胞8×107 /kg,1个月后,患者的染色体核型再次转为46,XY,患者至今无病存活50个月.结论 伊马替尼联合DLI对造血干细胞移植后CML复发具有一定的治疗效果.     

1,25-(OH)_2D_3对小鼠皮肤移植后脾T细胞亚群、MLR及NK细胞活性的影响

目的　探讨 1,2 5 二羟维生素D3 [1,2 5 (OH) 2 D3 ]抑制机体免疫功能的机理 ,为用于临床抗排斥治疗提供实验依据。方法　建立不同系小鼠间皮肤移植的动物模型。术日将实验小鼠随机分为四组 ,均用小鼠灌胃器给药。对照组 :每日 2 0ml/kg生理盐水 ;维生素D3 (VD3 )组 :单独应用 1,2 5 (OH) 2 D3 2 .5 μg·kg-1·d-1;环孢素A(CsA)组 :单独应用CsA 2 5mg·kg-1·d-1;VD3 +CsA组 :联合应用VD3 +CsA ,按VD3 组和CsA组用药剂量给药。术后 10d ,测定小鼠脾的T细胞亚群、单向混合淋巴细胞反应 (MLR)、自然杀伤细胞 (NK)活性。结果　VD3 组的移植皮片存活时间 (13.13±1.13)d ,明显长于对照组的 (9.75± 0 .89)d ;CD3+ 、CD4 + T细胞百分率 4 0 .19%± 4 .2 5 %、2 4 .6 5 %±3.4 7%均明显低于对照组 4 8.70 %± 7.19%、 33.5 5 %± 4 .34% ,P <0 .0 1;对BALB/C鼠的MLR(0 .95± 0 .12 )明显低于对照组 (1.19± 0 .2 2 ) ,P <0 .0 5 ;NK细胞的活性与对照组小鼠比较 ,差异无显著性。结论　 1,2 5 (OH) 2 D3 能延长小鼠皮肤移植的存活时间 ,其抑制机体免疫功能的作用是通过减少CD3+ 、CD4 + T细胞的数量及抑制T细胞功能而发挥的 ,对NK细胞活性无明显影响。     

门静脉预输注供者凋亡骨髓细胞延长大鼠移植心脏的存活时间

目的探讨门静脉输注供者的凋亡骨髓细胞对大鼠移植心脏存活时间的影响。方法以Wistar大鼠为供者、SD大鼠为受者,将其随机分为4组,每组15只,A组为对照组,受者术前6d经门静脉输注RPMI1640培养基0.5ml,术后不注射环孢素A(CsA);B组为骨髓细胞输注组,受者术前6d经门静脉输注供者的骨髓细胞5×107个,术后不用CsA;C组为凋亡细胞输注组,受者术前6d经门静脉输注供者的凋亡骨髓细胞5×107个,术后不用CsA;D组为CsA组,受者术前3d起腹腔注射CsA5mg/kg,直至术后10d。60Coγ射线照射诱导骨髓细胞凋亡,各组大鼠建立腹部异位心脏移植模型。观察各组移植心的存活时间、组织病理学改变,测定受者血清中白细胞介素10(IL-10)及转化生长因子β1(TGF-β1)的含量及单向混合淋巴细胞培养(MLR)结果。结果C组移植心的存活时间为(14.00±0.95)d,较A组明显延长(P<0.01),但仍未达到长期存活(存活时间短于CsA组)。术后7d,C组移植心组织切片呈现中度急性排斥反应,心肌细胞损害不明显,但有大量淋巴细胞浸润。除术后7d的TGF-β1外,C组其它各测定时点的血清IL-10及TGF-β1均高于其它3个组。C组大鼠的脾细胞在供鼠脾细胞的刺激下,细胞增殖反应明显低于A组、B组(P<0.01),而对第三品系大鼠的脾细胞仍有较强的增殖反应,具有明显的抗原特异性;CsA组的细胞增殖均被抑制。结论门静脉预输注供者的凋亡骨髓细胞,可明显延长大鼠移植心脏的存活时间,但单纯单剂量的输注凋亡细胞并不足以建立长期、稳定的免疫耐受。     

造血干细胞在皮肤移植中诱导特异性免疫耐受的研究

目的 探讨造血干细胞在皮肤移植中诱导特异性免疫耐受的作用和地位；尝试建立一种简单、有效且实用的耐受诱导方案。方法 采用小鼠皮肤移植模型；通过免疫磁珠法负筛选系统提取供者骨髓中的造血干细胞。给低剂量放射线全身照射的BALB／C小鼠管饲CsA 50mg／kg，接着经尾静脉推注冷藏的C57BL／6小鼠的造血干细胞或骨髓细胞，并当天完成C57BL／6小鼠→BALB／C小鼠的皮肤移植。记录皮肤存活时间并于30d后对受者小鼠作混合淋巴细胞反应(MIR)和迟发超敏反应(DTH)检查。结果 经处理的BALB／C小鼠移植皮肤存活时间延长；MLR和DTH检查证明BALB／C小鼠对C57BL／6小鼠的抗原生产了特异性耐受，但对无关第三者KM小鼠的抗原仍表现出强烈的免疫应答。输注骨髓细胞和造血干细胞的两个方案差异无显著性。结论 利用C57BL／6小鼠的造血干细胞在BALB／C小鼠体内成功诱导出了供者特异性的移植耐受；输注骨髓细胞和造血干细胞的两个方案差异无显著性。     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Development of Selective Low-Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL-Specific Adsorption for LDL Apheresis System

Abstract: Low-density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL-lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im-munoadsorbent utilizing an anti-LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL-removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion-rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 10⁴ daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high-density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL-binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow-fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.     

Artificial organs 2010: a year in review

In this Editor's Review, articles published in 2010 are organized by category and briefly summarized. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, and the International Society for Rotary Blood Pumps, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level."Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide such meaningful suggestions to the author's work whether eventually accepted or rejected and especially to those whose native tongue is not English. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, Wiley-Blackwell, for their expert attention and support in the production and marketing of Artificial Organs. In this Editor's Review, that historically has been widely received by our readership, we aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. We look forward to recording further advances in the coming years.     

Avaliação do clube de revista de anestesiologia por meio de mudanças semânticas

Background and objectives

The interactive approach of a journal club has been described in the medical education literature. The aim of this investigation is to present an assessment of journal club as a tool to address the question whether residents read more and critically.

Methods

This study reports the performance of medical residents in anesthesiology from the Clinics Hospital – University of São Paulo Medical School. All medical residents were invited to answer five questions derived from discussed papers. The answer sheet consisted of an affirmative statement with a Likert type scale (totally disagree–disagree–not sure–agree–totally agree), each related to one of the chosen articles. The results were evaluated by means of item analysis – difficulty index and discrimination power.

Results

Residents filled one hundred and seventy three evaluations in the months of December 2011 (n = 51), July 2012 (n = 66) and December 2012 (n = 56). The first exam presented all items with straight statement, second and third exams presented mixed items. Separating “totally agree” from “agree” increased the difficulty indices, but did not improve the discrimination power.

Conclusions

The use of a journal club assessment with straight and inverted statements and by means of five points scale for agreement has been shown to increase its item difficulty and discrimination power. This may reflect involvement either with the reading or the discussion during the journal meeting.     

Lymphocytapheresis

Abstract: Leukocytapheresis has long been performed with the centrifugal method. But in 1989 in Japan, the Asahi Medical Co. developed the extracorporeal leukocyte-removal filter, Cellsorba. This filter consists of non-woven fabric, which can remove leukocytes from whole blood during extracorporeal circulation. In the incipient stage, this filter was applied to collagen diseases, rheumatoid arthritis, and systemic lupus erythematosus. During the following studies, this filter has been found to have an immunosuppressive effect. Now, it is beginning to be applied to various kinds of autoimmune diseases. Moreover, this filter has recently been recognized to be effective in inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. The outline of Cellsorba and the application of this filter is described here.     

Soluble TNFα Receptors Are Increased in Chronic Renal Insufficiency and Hemodialysis and Inhibit Neutrophil Priming by TNFα

Abstract: The oxidative burst of neutrophils from azotemic patients is refractory to priming by tumor necrosis factor-α (TNFα). Soluble TNFα binding proteins (TNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNFa priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNFa priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sTNFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNFα primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNFα in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNFα priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.