同种输血对食管癌患者一氧化氮生成的影响

目的　探讨同种输血对食管癌手术患者一氧化氮 (NO)生成的影响。方法　食管癌手术患者 18名 ,以输注去白细胞血液的食管癌手术患者为实验对照 ,以 2 0名健康志愿者为正常对照 ,采用硝酸还原酶法检测血清中NO3 -/NO2 -来反映NO生成水平。结果　①食管癌患者的血清中NO3 -/NO2 -浓度与正常人相比无差异。②实验组输血后第 1天与输血前相比血清中NO明显降低 (P <0 .0 1) ,并显著低于实验对照组 (P <0 .0 1)。结论　食管癌患者围手术期同种输血可导致血清中NO浓度降低 ,而输注去白细胞血液患者血清中NO浓度下降不明显。因此 ,食管癌患者围手术期输注去白细胞血液明显优于输注常规血液     

不同输血方式对肺鳞癌患者围术期TNF—α和IL—lO的影响

[目的]探讨同种输血和自体输血对肺鳞癌患者围术期肿瘤坏死因子-α(TNF-α)和白细胞介素—10(IL—10)的影响和相互关系。[方法]2001年1月至2003年1月对31例肺鳞癌患者行肺癌根治术，将其分为两组，同种输血组(A组)17例，自体输血组14例(B组)。测定两组围术期血清中TNF-α和IL—10的浓度。[结果]A组输血后d1与输血前相比血清中TNF-α、IL-10浓度增高，以IL—10变化尤为明显，输血后d5TNF-α降低并接近输血前的水平，明显低于B组，IL—10仍明显高于输血前的水平。B组中不同时问IL—10无显著变化，TNF-α于ds明显高于输血前。[结论]肺鳞癌患者围术期同种输血后血清中TNF-α降低与IL—10升高有关，IL—10升高可能是同种输血后免疫抑制的重要原因。自体输血可减轻或去除这一作用。     

不同输血方式对肺鳞癌患者围术期TNF-α和IL-10的影响

〖目的〗探讨同种输血和自体输血对肺鳞癌患者围术期肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL10)的影响和相互关系.〖方法〗2001年1月至2003年1月对31例肺鳞癌患者行肺癌根治术,将其分为两组,同种输血组(A组)17例,自体输血组14例(B组).测定两组围术期血清中TNF-α和IL-10的浓度.〖结果〗A组输血后d1与输血前相比血清中TNF-α、IL-1O浓度增高,以IL-10变化尤为明显,输血后d5TNF-α降低并接近输血前的水平,明显低于B组,IL-1O仍明显高于输血前的水平.B组中不同时间IL-10无显著变化,TNF-α于d5明显高于输血前.〖结论〗肺鳞癌患者围术期同种输血后血清中TNF-α降低与IL-10升高有关,IL-10升高可能是同种输血后免疫抑制的重要原因.自体输血可减轻或去除这一作用.     

急性与慢性再生障碍性贫血患者IL-4、IFN-γ及TNF-α诱生水平的对比研究

目的　检测急性和慢性再生障碍性贫血 (再障 )患者骨髓单个核细胞 (BMMNC)培养上清白细胞介素 4(IL 4)、γ干扰素 (IFN γ)及肿瘤坏死因子α(TNF α)的诱生水平 ,了解两组患者免疫学状况的异同点。方法　利用双抗体夹心ELISA法测定BMMNC培养上清中IL 4、IFN γ和TNF α的诱生水平 ,比较两组患者上述细胞因子水平的差异。结果　①所有患者IFN γ、TNF α水平均增高 ,与对照组比较 ,差异有显著性。急性组IL 4大致正常 ,与对照组比较 ,差异无显著性 ;慢性组IL 4水平升高 ,与对照组比较 ,差异有显著性。②在急、慢性组之间 ,TNF α水平差异无显著性 ;但IL 4、IFN γ水平差异有显著性。结论　异常细胞免疫效应可能在急性再障发病中起主要作用 ;慢性再障既可能有细胞免疫增强 ,又有体液免疫功能亢进。     

细胞因子的检测在肾移植术后急性排斥反应的诊断价值

目的　探讨TNF α、IL 6在肾移植术后急性排斥反应、感染、CsA肾毒性时的变化。方法　采用ELISA法 ,动态监测 10 6例患者移植前后血清TNF α、IL 6及尿液TNF α的变化。结果　肾移植术前TNF α、IL 6与对照组无显著性差别 ,术后第 1天明显升高 ,TNF α与IL 6分别于 1w及 2w左右降至术前水平。急性排斥反应前 1～ 3d血清TNF α、IL 6及尿液TNF α即有不同程度升高 ,抗排斥治疗有效后迅速下降。并发感染时血清TNF α、IL 6显著升高 ,尿液TNF α无升高 ,CsA肾毒性时均无明显变化。结论　结合临床动态监测血清TNF α、IL 6及尿TNF α可做为辅助诊断急性排斥反应的免疫生物学指标。     

慢性病贫血患者细胞因子变化的研究

目的　探讨肿瘤坏死因子α(tumornecrosisfactor α,TNF α)、干扰素γ(interferonγ ,INF γ)、白细胞介素 6 (interleukin 6 ,IL 6 )在慢性病贫血 (anemiaofchronicdiseases ,ACD)发生机制中的作用。方法　测定31例ACD患者的铁代谢指标 (血清铁、血清铁蛋白、骨髓铁 ) ,采用双抗体酶联免疫吸附法 (ELISA)检测ACD患者血清中TNF α、INF γ、IL 6。结果　与对照组比较 ,ACD组血清中TNF α、INF γ、IL 6均显著增高 (P <0 0 1)。TNF α、IL 6与血清铁、血红蛋白浓度呈负相关。结论　免疫及炎症反应所产生的细胞因子INF γ、TNF α、IL 6等可能通过干扰铁代谢和抑制EPO(erythropoietin)生成、钝化对EPO的反应等途径介导了慢性病贫血的发生和发展过程     

肺癌患者外周血有核细胞IL-2R、TNF-α及IFN-γ表达的检测及其临床意义

目的　探讨肺癌患者外周血有核细胞IL 2R(CD2 5 )、TNF α和IFN γ的表达规律及其临床意义。方法　用流式细胞术对 118例肺癌患者外周血表达IL 2R、TNF α和IFN γ有核细胞的检出率进行检测和分析。结果　肺癌患者IL 2R、TNF α和IFN γ的表达率显著高于正常对照组 (P <0 .0 1) ,但其中未化疗者与正常对照组无显著性差异 (P >0 .0 5 ) ;化疗者表达率均显著高于未化疗者 (P <0 .0 1) ;在未化疗的患者中 ,伴转移者外周血有核细胞的IL 2R、TNF α和IFN γ的检出率均显著低于未转移者 (P <0 .0 1或P <0 .0 5 )。结论　肺癌患者外周血有核细胞的IL 2R、TNF α和IFN γ表达的检测有助于化疗机制的解释和病人预后的判定     

围术期自体输血对血清炎症性细胞因子及免疫球蛋白水平变化的影响

目的　外科手术自体血回输对患者血清炎症性细胞因子白介素 1β(IL 1β)、白介素 6(IL 6)、白介素 8(IL 8)、肿瘤坏死因子 α(TNF α)及免疫球蛋白IgA、IgG、IgM的影响。方法　30名手术患者,随机分为两组:自体血回 输组15名;异体输血组15名。两组均于麻醉前、术后1天、术后7天采外周静脉血5ml,离心后取血清2ml于低温 冰柜保存待检。结果　术后1天IgA、IgG两组均降低,IL 6、IL 8、TNF α两组均升高,但两组差异有显著性,P< 0.05;术后7天与术前相比,两组差异有显著性,P<0.05;IL 1β、IgM两组变化不显著,差异无显著性,P>0.05。 结论　炎症性细胞因子IL 6、IL 8、TNF α及免疫球蛋白IgA、IgG在自体输血、异体输血后变化有显著差异。自体 输血对患者免疫功能影响较小,异体输血抑制了患者术后抗感染及伤口愈合等能力,对免疫功能抑制明显。     

亚低温对多发伤患者血清中细胞因子的影响及临床意义

目的探讨亚低温对多发性创伤患者血清中肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的影响及临床意义。方法采用酶联免疫吸附法 (ELISA)监测 38例多发性创伤患者在亚低温治疗期间外周血清TNF α、IL 1β、IL 6、IL 10在伤后即刻、d3 、d5、d9的动态变化 ,并以 30例常规治疗的多发性创伤患者作为对照组进行对比分析。结果亚低温治疗组患者血清TNF α、IL 1β、IL 6、IL 10浓度比常规治疗组明显降低 (P <0 .0 5 )。结论亚低温治疗能够降低多发性创伤患者血清中细胞因子浓度 ,从而推测可能会减少患者多脏器功能不全综合征发生率     

吲哚美辛联合干扰素治疗慢性乙型肝炎患者的疗效及其机理初探

目的　探讨吲哚美辛 (INDO)联合干扰素治疗慢性乙型肝炎的疗效及其对血清细胞因子分泌模式的调节作用。方法　 78例慢性乙肝患者随机分为两组 ,分别以干扰素 α(IFN α)和IFN α INDO治疗 6个月。观察治疗前后血清IFN γ、IL 4及IFN γ/IL 4比值水平的变化。结果　慢性乙肝患者血清IFN γ及IFN γ/IL 4均明显低于正常对照组 ,IL 4明显高于正常对照组 ,治疗后所有患者均有IFN γ、IFN γ/IL 4的升高及IL 4的降低 ,且IFN INDO组较IFN组变化趋势更加明显 (P <0 .0 5 ) ;IFN INDO组临床有效率明显好于IFN组 (P <0 .0 5 )。结论　吲哚美辛在慢性乙肝治疗过程中能提高IFN α抗病毒能力 ,其机制似与调节T应答模式向Th1/Tc1应答转变有关。     

结肠癌患者自体瘤细胞对不同来源淋巴细胞功能的影响

目的 :研究结肠癌患者自体瘤细胞对肿瘤浸润淋巴细胞、肿瘤引流淋巴结的淋巴细胞、外周血淋巴细胞的影响。方法 :比较结肠癌患者自体肿瘤细胞对体外培养TIL、PBL、LNL细胞增殖、诱生细胞因子 (IL - 2、TNFα、IFNγ)水平的影响。结果 :发现结肠癌患者的TIL和PBL、LNL相比 ,CD8+细胞增加 ,CD4+细胞数减少。PBL和LNL对PHA、rhIL - 2刺激产生的细胞增殖能力比TIL强。PBL能产生较高水平的TNFα 和IFNγ,而IL - 2产生水平较低 ;LNL产生高水平的TNFα 和IL - 2 ,但仅产生低水平的IFNγ。TIL产生的TNFα、IFNγ 水平较PBL、LNL低。实验结果表明结肠癌患者自体肿瘤细胞对不同来源淋巴细胞的细胞因子分泌有不同影响 ,其机制有待进一步研究。     

人外周血NKT细胞体外扩增及其分泌细胞因子的研究

目的　建立人外周血自然杀伤T细胞 (NKT)体外扩增及检测NKT细胞所分泌的细胞因子的方法。方法　分别采用单加α 半乳糖神经酰胺 (α Galcer组 ) ,单加树突状细胞 (DC组 )以及同时加α Galcer、DC(α Galcer、DC组 )的方法从人外周血单个核细胞 (PBMC)和纯化T淋巴细胞中扩增TCRVα2 4+ /TCRVβ1 1 + NKT细胞。采用细胞内细胞因子流式细胞术检测手段测定NKT细胞中IL 4 ,IFN γ、TNF α阳性细胞比例。结果　PBMC中的α Galcer组 ,DC、α Galcer组和纯化T淋巴细胞中的DC、α Galcer组 ,NKT细胞扩增 1 9d后分别占淋巴细胞的 (2 5 .5± 7.2 ) %、(1 8.2± 8.2 ) %和 (2 4 .8± 5 .5 ) % ,NKT细胞分别扩增了 (1 5 .1± 9.1 )× 1 0 3 倍、(2 1 .8± 1 7.3)× 1 0 3 倍和 (2 3.0± 1 6 .7)× 1 0 3 倍 ,与其它各组差异有显著性意义 (P <0 .0 1 )。扩增过程TCRVβ1 1+ NKT细胞中分泌IL 4 ,IFN γ和TNF α的细胞比例均高于TCRVβ1 1 T淋巴细胞 (P <0 .0 5 )。结论　α Galcer具有体外大量扩增NKT细胞的能力 ,同时α Galcer的激活能力受CD1d分子的限制。由于PBMC中的单核系细胞也表达CD1d分子 ,因此直接从PBMC扩增NKT也能获得良好的效果     

The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial

Allogeneic blood transfusions in surgical patients have been associated with an increased risk of infectious complications and organ dysfunction. Residual leukocytes contaminating units of packed red blood cells have been incriminated through the induction of anergy and/or a potentiated inflammatory response, leading to the possibility that leukoreduced red blood cell transfusion might mitigate these effects. We set out to evaluate the effect of leukoreduced red cell transfusion on the risk of infections complications in patients requiring transfusion following injury. We conducted a single-center, double-blinded randomized controlled trial of leukoreduced versus standard, nonleukoreduced red blood cell transfusions in injured patients receiving transfusion within 24 hrs of injury. The primary endpoint was infectious complications within 28 days of randomization. Secondary end points were multiple organ failure, length of stay, febrile episodes, and mortality. Two hundred sixty eight subjects were eligible for analysis. Rates of infectious complications were similar in subjects receiving leukoreduced transfusions (30%) or standard transfusions (36%) ([RR], 0.84 [0.55-1.3]) and there was no statistically significant effect of leukoreduced blood transfusion on mortality [RR, 1.20 (0.74-1.9)], febrile episodes [RR, 1.01 (0.89-1.2)], or organ dysfunction scores (5.9 vs. 6.6; P=0.29). Thus, pre-storage leukoreduction of allogeneic red blood cells had a small, but non-significant effect on the rate of infectious complication in this high-risk population requiring transfusion. There was no effect on the rates of febrile episodes, mortality, length of stay, or severity of organ dysfunction.     

Mannose-binding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions

BACKGROUND: Serum levels of mannose-binding lectin (MBL), a recognition molecule of the lectin pathway of complement, are highly variable, based on genetic variation. After cardiac surgery, extracorporeal circulation and ischemia-reperfusion injury initiate a systemic inflammatory response, which can evolve to multiple organ dysfunction syndrome (MODS). Preoperative transfusions of allogeneic white blood cells (WBCs) contribute to infectious and inflammatory complications. This study investigates the role of MBL in relation to blood transfusions and complications after cardiac surgery. STUDY DESIGN AND METHODS: In cardiac surgery patients who participated in a randomized trial comparing leukoreduced with buffy coat-depleted red blood cell (RBC) transfusions, circulating MBL was measured pre- and postoperatively by enzyme-linked immunosorbent assay (ELISA). Data were related to the incidence of complications and to the transfusions the patients received. RESULTS: Patients with high preoperative serum MBL levels (>400 ng/mL) show a significant (52 +/- 12%) decrease of serum MBL postoperatively, whereas patients with low serum MBL levels (< or =400 ng/mL) show a significant increase of serum MBL levels after surgery (140 +/- 106%), which was further enhanced by fresh-frozen plasma (FFP) transfusions. MBL levels were not associated with infections, sepsis, or death. Patients with MBL deficiency (MBL < or = 80 ng/mL) were protected against development of MODS (p = 0.016), whereas FFP transfusion abolished this protection (p = 0.048). CONCLUSION: Cardiac surgery is associated with MBL consumption, independent of the transfusion of allogeneic WBCs. Patients with MBL deficiency develop no MODS, unless they have been transfused with FFP, which is associated with MBL reconstitution. Therefore, sustained MBL deficiency may be a favorable status for patients undergoing cardiac surgery.     

白细胞过滤对血小板保存期间炎性细胞因子水平的影响及临床效果的评估

目的　考察浓缩血小板悬液 (plateletconcentratesuspend ,PCs)在保存期内IL 1β、IL 6、IL 8和TNF α的浓度变化和过滤对其的影响 ,了解在保存前滤除PCs中的白细胞是否能有效地减少这些细胞因子的积累和降低受血者非溶血性发热性输血反应 (febrilenonhemolytictransfusionreactions,FNHTR)发生率。 方法　将 1单位PCs分成两等份 ,分别给予血小板专用白细胞滤器过滤处理和不滤除白细胞处理 ,保存 5d。在 0、3、5d测定IL 1β、IL 6、IL 8和TNF α含量及白细胞计数 ,采用配对t检验进行统计分析 ;临床观察未滤组和过滤组PCs输后FNHTR发生率。结果　PCs中的白细胞计数与保存 5d时IL 1β、IL 6、IL 8和TNF α水平之间呈正相关。未滤组PCs中有较多白细胞混入 [(35 1± 81)× 10 6/袋 ],在保存期间IL 1β、IL 6、IL 8和TNF α水平明显升高 ;过滤组的PCs残余白细胞 <1× 10 6/袋在保存期间诸细胞因子均保持在 0d水平 ;临床观察显示 ,末滤PCs与过滤PCs输注后FNHTR发生率分别为 2 0 .83%和 5 .83% ,P <0 .0 1。结论　保存前用血小板专用去白细胞滤器去除PCs中残留的白细胞能有效地防止细胞因子的积累 ,同时保留 95 %以上的血小板。输注滤除白细胞的PCs能有效地减少FNHTR发生     

Blood transfusion and total joint replacement surgery: T helper 2 (TH2) cytokine secretion and clinical outcome

Surgery and blood transfusions have both been reported to cause decreases in various measures of cell-mediated immunity. A study of in vitro T helper lymphocyte type 2 (Th2) cytokine secretion after major joint replacement surgery was performed because these cytokines (IL4 and IL10) generally down-regulate cellular immune function. Th1 cytokines such as IL2 tend to up-regulate cellular immunity. Forty-three patients undergoing elective joint replacement surgery had pre- and multiple post-operative levels of IL2, IL4 and IL10 secretion measured and analysed with regard to demographic and clinical outcome data. Total joint replacement alone without allogeneic transfusions led to substantial increases in peak mean IL4 (2.1 times the pre-operative level) and IL10 secretion in vitro (4.3-fold) compared with much more modest increases in IL2 (1.36-fold) ( P  < 0.0001 for changes from baseline for each cytokine). In 14 patients who received allogeneic transfusions, these changes were greater than those in recipients of only autologous blood for IL4 (5.0-fold; P  = 0.0036 vs. no allogeneic transfusion) and IL10 (15.7-fold; P  = 0.079) but not for IL2 (1.38-fold; P  = 0.38). The dramatic increase in Th2 cytokine secretion and minimal change in Th1 cytokine secretion after total joint replacement, with or without allogeneic transfusions, was seen regardless of type of anaesthetic, duration of surgery or whether knee or hip replacement occurred. These changes in cytokine patterns may contribute to the decreases in cellular immune function seen after surgery. Allogeneic transfusions but not autologous transfusions appear to exacerbate this immune deviation toward a T helper 2 (Th2) type response, and thus probably contribute to down-regulation of cellular immunity in the setting of joint replacement surgery.     

Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe

BACKGROUND: The purpose of this study was to assess current practices in blood management in elective orthopedic surgery in Europe. STUDY DESIGN AND METHODS: For this 225-center prospective survey, data were collected on 3996 patients. Actual perioperative blood loss was compared to preoperative estimates. Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated. The probability of allogeneic transfusion based on selected predictor variables was estimated. RESULTS: A total of 2640 (67%) hip and 1305 (33%) knee arthroplasty patients were evaluated. Estimated blood loss (median, 750 mL) was significantly lower than computed blood loss (median, 1944 mL). A total of 2762 (69%) patients received transfusions, including 1393 (35%) autologous-only and 1024 (25%) allogeneic-only. The probability of allogeneic transfusion decreased with increasing baseline Hb, but differentially so for men and women. Transfusion triggers were Hb levels of 8.93 +/- 1.83 g per dL for allogeneic transfusions, and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate (1%) of wound infections than allogeneic blood transfusion (4.2%). CONCLUSION: Accurate assessment of preoperative Hb levels, better estimation of perioperative blood loss, efficient use of autologous blood, adherence to transfusion guidelines, and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management.     

Absence of transfusion-associated microchimerism in pediatric and adult recipients of leukoreduced and gamma-irradiated blood components

BACKGROUND: Transfusion‐associated microchimerism (TA‐MC), the persistence of significant levels of donor white blood cells (WBCs) in blood recipients for prolonged periods, has been demonstrated after nonleukoreduced and leukoreduced transfusion to patients with severe traumatic injury. Development of TA‐MC has not been rigorously studied in settings that do not involve massive trauma where the blood is leukoreduced and irradiated. STUDY DESIGN AND METHODS: A cohort of 409 prospectively followed medical and surgical adult and pediatric female recipients of leukoreduced and mostly irradiated allogeneic red blood cell and platelet transfusions were evaluated to determine development of TA‐MC. Four‐ and 8‐weeks‐posttransfusion samples were analyzed using quantitative real‐time polymerase chain reaction for Y‐chromosome sequences in WBC DNA, the marker for microchimeric cells in female blood recipients. Repeat testing was performed on Y‐chromosome–positive samples to confirm microchimerism (MC), and subsequent posttransfusion samples were tested to investigate persistence of MC. RESULTS: On initial testing, 40 of 207 (19%) adult and 44 of 202 (22%) pediatric female blood recipients demonstrated low‐level MC. On repeat testing of these and additional specimens, 12 (3%) recipients demonstrated low‐level transient MC, but none had persistent TA‐MC similar to that seen in transfused trauma patients. CONCLUSION: Persistence of MC was not demonstrated in adult and pediatric recipients of leukoreduced and mostly irradiated blood components. The risk of TA‐MC appears to be dependent on the clinical setting and is rare other than in patients sustaining severe traumatic injury.     

Th1 and Th2 subsets in orthopaedic surgery by single-cell cytokine analysis

Significant immunosuppression can occur following allogeneic blood transfusion or surgery. Cytokine stimulation controls immune responses and determines their type and intensity. Infusion of autologous or allogeneic blood provides elements, including cytokines, which may result in transfusion-associated immunomodulation. This study investigates to what extent autologous/cell salvage transfusions affect levels of intracellular cytokines interferon-gamma and interleukin-4, and if this indicates a shift in the T-helper 1/T-helper 2 cell ratio using a novel method of detecting intracellular cytokines, the Magnetic Activated Cell Sorter Cytokine Secretion Assay (MACS Assay). Comparisons were made between patients receiving autologous blood or no blood transfusion, for pre- and post-operation levels of interferon-gamma and interleukin-4. Interferon-gamma producing T-helper 1 cells decreased post-operatively. Concomitantly, interleukin-4 producing T-helper 2 cells increase. These results demonstrate a measurable shift from T-helper 1 to T-helper 2 cells post-operatively. Secondly, the study showed surgery alone instigates the same level of immunomodulation as autologous/cell salvage blood transfusion in combination with surgery.