口饲乳果糖对失血性休克大鼠预后的影响

为了进一步阐明失血性休克预后与继发性内源性内毒素血症的直接关系，作者探讨了用口饲乳果糖清除肠道内毒素对大鼠失血性休克的保护作用。造成休克前，首先给大鼠口腔管饲２０％乳果糖（５ｍｌ／ｄ）或等容量生理盐水７天，每天给药２次。结果：休克后４８ｈ，乳果糖组大鼠存活率要明显高于盐水组（１０／１０与４／９，Ｐ＜０．０１）。休克后９０ｍｉｎ和１２０ｍｉｎ，乳果糖组大鼠血浆内毒素、ＴＮＦ水平均显著低于盐水组。提示：继发于失血性休克的内源性内毒素血症及肿瘤坏死因子在促使休克向不可逆性发展中可能起重要作用。作者认为，临床上对严重的失血性休克患者，除作复苏外，还应针对感染，尤其是内毒素血症尽早采取防护措施。     

内毒素血症细胞因子一氧化氮在重度失血性休克发展中的作用

目的　探讨内毒素血症、细胞因子、ＮＯ在重度失血性休克发展过程中的作用和机制。方法　选用大白兔２６只，分为失血性休克组（１４ 只），对照组（１２ 只），休克组观察休克前后血浆内毒素、ＴＮＦα、ＩＬ－ ６、ＩＬ－８、ＮＯ的动态变化，对照组观察手术前后上述指标的变化，两组动物均观察２４ 小时、４８ 小时存活率。结果　大白兔发生失血性休克后血浆内毒素、ＴＮＦα、ＩＬ－６、ＩＬ－８ 、ＮＯ的水平与休克前及对照组比较有明显升高，死亡动物中血浆上述物质水平显著高于存活动物。结论　内毒素血症、细胞因子、ＮＯ等发挥重要的协同作用，促使失血性休克向不可逆方向进展。     

内毒素血症中降钙素基因相关肽对肿瘤坏死因子所致血流动力学改变的影响

探讨在内毒素血症和内毒素休克时肿瘤坏死因子（ＴＮＦ）影响血流动力学的效应是否与降钙素基因相关肽（ＣＧＲＰ）的释放和作用有关。将５６只ＳＤ大白鼠随机分成４组，每组１４只。各组分别经中心静脉注射生理盐水（对照组）、内毒素（实验１组），重组ＴＮＦ（实验２组）和抗ＴＮＦ单抗（ＣＢ０００６）＋内毒素（实验３组）。１小时后测定各组动物的血浆ＣＧＲＰ含量，并测量血流动力学指标。结果：与对照组相比较，各实验组动物的血浆ＣＧＲＰ含量分别增加约７．１倍、６．７倍和５．５倍（Ｐ值均＜０．０１），与此同时各实验组动物平均动脉压（ＭＡＰ）分别显著降低４０．０％、３０．８％和２５．９％，心输出量（ＣＯ）亦分别减少约２０．０％、２８．３％和１５．１％（Ｐ值均＜０．０１）。与对照组动物的总末梢血管阻力（ＴＰＲ）相比，实验１组和３组的动物分别显著降低约２５．９％和１６．３％（Ｐ值均＜０．０１）。结论：内毒素血症时ＣＧＲＰ在ＴＮＦ所致血流动力学改变过程中具有一定的作用     

脾切除对内毒素诱生肿瘤坏死因子α和白介素6的影响

：目的：观察脾切除对内毒素诱生肿瘤坏死因子 α（ＴＮＦ α）、白介素 ６（ＩＬ ６）的影响及己酮可可碱（ＰＴＸ）的抑制效应。方法：制备脾切除大鼠内毒素血症模型，动物随机分为有脾组（５６ 只）、无脾组（５６只）、ＰＴＸ治疗组（１６ 只）。采用酶联免疫吸附法检测伤前和伤后不同时间点血清ＴＮＦ α和ＩＬ ６含量。结果：脾切除后大鼠内毒素血症时血清ＴＮＦ α水平明显升高，而ＩＬ ６ 水平明显下降，与有脾组比较有显著性差异（Ｐ均＜０．０５）。脾切除大鼠给予ＰＴＸ治疗，血清ＴＮＦ α峰值下降，１．５小时和４ 小时分别下降了３５．２％ （Ｐ＜ ０．０５）和１７．２％ ，而ＰＴＸ对血清ＩＬ ６ 水平无明显影响。结论：脾切除可显著影响机体内毒素介导细胞因子的产生，炎症介质调节机制异常可能与脾切除后凶险性感染的发生有关；ＰＴＸ对脾切除后内毒素血症机体细胞因子的产生具有选择性抑制作用。     

复方丹参注射液对兔内毒素休克的防治作用

目的：通过测定兔内毒素休克时肿瘤坏死因子（ＴＮＦ）和自由基的变化，探讨复方丹参注射液对兔内毒素休克的防治作用。方法：健康家兔２４只随机分为３组，每组８只。对照组（Ａ组）输入与其它２组等量的０．９％氯化钠液；内毒素组（Ｂ组）静注精制内毒素；防治组（Ｃ组）于注入内毒素前输入复方丹参注射液。实验期间定时测定ＴＮＦ、丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）活性，同时监测平均动脉压（ＭＡＰ）、心率（ＨＲ）和计实验７小时兔存活数。结果：在整个实验时间内，Ａ组各项指标均保持稳定（Ｐ均＞０．０５）；Ｂ组ＴＮＦ和ＭＤＡ均升高（Ｐ均＜０．０５），ＳＯＤ活性降低（Ｐ均＜０．０５），ＭＡＰ、ＨＲ均下降（Ｐ均＜０．０５）；Ｃ组ＴＮＦ和ＭＤＡ升高程度均远低于Ｂ组（Ｐ均＜０．０５），ＳＯＤ活性保持稳定（Ｐ均＞０．０５）；实验７小时Ａ、Ｃ组各存活８只兔，而Ｂ组仅存活１只兔。结论：ＴＮＦ及自由基均参与了内毒素休克病理变化过程；复方丹参注射液能明显降低ＴＮＦ的增加幅度，减轻自由基造成的脂质过氧化作用，并能对抗内毒素休克时ＳＯＤ活性降低现象，使实验兔的７小时存活数显著提高     

大鼠严重烫伤并发心肌损害时肿瘤坏死因子的变化

目的：探讨炎症介质在严重烧伤后心肌损害中的作用。方法：采用大鼠３０％ 体表面积Ⅲ度烫伤模型,随机分为对照组（１０ 只）和烫伤组（５０ 只）,于烫伤后１、３、６、１２ 和２４ 小时检测大鼠血浆肿瘤坏死因子（ＴＮＦ）和肌钙蛋白Ｔ（ＴｎＴ）及心肌组织中ＴＮＦ的含量。结果：烫伤后６ 小时血浆ＴＮＦ水平〔（３．３８±０．９０）μｇ／Ｌ〕较正常对照组〔（１．０８±０．０１）μｇ／Ｌ〕显著升高（Ｐ＜ ０．０１）,１２ 小时达峰值〔（８．０２±１．０５）μｇ／Ｌ〕,伤后２４ 小时〔（６．４４±１．４３）μｇ／Ｌ〕虽有所下降,但仍显著高于正常对照组（Ｐ＜ ０．０１）。心肌组织ＴＮＦ含量伤后１２ 小时〔（２．１５±０．０９）ｎｇ／ｍ ｇ〕显著高于正常对照组〔（０．８８±０．０１）ｎｇ／ｍ ｇ,Ｐ＜ ０．０１〕。血浆ＴＮＦ水平与反映心肌损伤的敏感指标血浆ＴｎＴ的变化密切相关。结论：炎症介质ＴＮＦ在烧伤后心肌损害的发生发展中起重要作用     

内毒素性播散性血管内凝血家兔血浆肿瘤坏死因子水平的变化

采用间隔２４ｈ静脉注射内毒素（ＬＰＳ）的方法，给家兔诱导全身性施瓦茨曼反应（ＧＳＲ），以此作为家兔内毒素性播散性血管内凝血（ＤＩＣ）模型。在造模前后不同时间采用ＥＬＩＳＡ方法测定血浆肿瘤坏死因子（ＴＮＦ）水平。结果：在第１次注射ＬＰＳ后２ｈ血浆ＴＮＦ水平最高（７６．１８±２３．１８ｕｇ／Ｌ），其次为第２次注射ＬＰＳ后６ｈ（６６．９７±２４．７５ｕｇ／Ｌ）和１２ｈ（５７．９０±２１．５０ｕｇ／Ｌ，均较实验前（２１．６０±５．９９ｕｇ／Ｌ明显升高（Ｐ＜０．０１）。作者初步讨论了不同时相出现ＴＮＦ高峰的可能机制。     

新生儿休克时血浆肿瘤坏死因子的测定及其意义

目的：探讨肿瘤坏死因子（ＴＮＦ）在新生儿休克中的作用。方法：应用放射免疫方法检测３６例新生儿休克患儿血浆ＴＮＦ水平。结果：休克组治疗前血浆ＴＮＦ浓度〔（６０４．２６±１．２６）ｎｇ／Ｌ〕显著高于正常对照组〔（３２８．３８±１．１５）ｎｇ／Ｌ〕，Ｐ＜０．０１；感染性休克组〔（６５６．１４±１．４６）ｎｇ／Ｌ〕高于非感染性休克组〔（４６８．７９±１．３２）ｎｇ／Ｌ〕，Ｐ＜０．０５；死亡组〔（６８６．１３±１．１９）ｎｇ／Ｌ〕高于存活组〔（４７１．２３±１．２９）ｎｇ／Ｌ〕，Ｐ＜０．０５。血浆ＴＮＦ浓度与患儿器官损伤数呈正相关趋势，ｒ＝０．３１，Ｐ＞０．０５。结论：ＴＮＦ参与新生儿休克的病理生理过程，且与休克预后有关     

危重病患者血肿瘤坏死因子和白细胞介素6水平的研究

对６０例急性危重病患者血肿瘤坏死因子（ＴＮＦ－α）和白细胞介素６（ＩＬ－６）水平测定发现，ＴＮＦ－α含量在心衰组和中毒性休克组较正常对照显著升高（ｐ＜０．０５，ｐ＜０．０１）；在急性心肌梗塞组合并心源性休克和脑卒中组出现大量脑出血或大面积脑梗塞时，患者血浆ＴＮＦ－α含量与对照组相比亦显著升高（ｐ＜０．０５）。四组病人血中均存在高水平的ＩＬ－６（ｐ＜０．０１）。结果提示，ＴＮＦ－α和ＩＬ－６均参予了某些危重病的发病过程。     

免疫吸附清除循环肿瘤坏死因子α对内毒素休克兔肠道改变的影响

目的：用抗肿瘤坏死因子α（ＴＮＦα）单克隆抗体（ＭｃＡｂ）免疫吸附法特异性清除循环ＴＮＦα,观察其对内毒素休克兔肠道改变的影响。方法：以致死剂量内毒素（８×１０９ＣＦＵ／ｋｇ）制成内毒素休克兔模型后分为对照组（ｎ＝７）及免疫吸附组（ｎ＝１０）。６０分钟后开始体外循环免疫吸附,监测平均动脉压（ＭＡＰ）,观察２组循环ＴＮＦα水平。３６０分钟活杀动物,取小肠行组织病理检查。结果：①免疫吸附组血液灌流后９０分钟ＭＡＰ开始回升〔（１１．６±１．４）ｋＰａ,１ｋＰａ＝７．５ｍｍＨｇ〕,此后一直高于对照组（Ｐ均＜０．０５）。②免疫吸附组１２０分钟以后ＴＮＦα活性均较对照组明显降低（Ｐ均＜０．０５）。③免疫吸附组肠粘膜损害程度较对照组明显减轻。结论：抗ＴＮＦαＭｃＡｂ特异性免疫吸附方法能有效清除循环ＴＮＦα,减轻肠道的病理损害。其可望成为临床治疗内毒素休克合并多脏器损害的新途径     

A Pilot Study of the Predictive Value of Plasma Tumor Necrosis Factor α. and Interleukin 1β for Streptococcus pneumoniae Bacteremia in Febrile Children

Objective : To determine the value of tumor necrosis factor α (TNF) and interleukin 1β (IL1) levels in predicting Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children who do not have a bacterial source for their fever on physical examination. Methods : A prospective, nested case-control study was conducted in a children's hospital ED. All febrile children <3 years old who were believed to be immunocompetent and not in shock, had no obvious bacterial source for their fever on physical examination, and had a blood culture obtained were eligible. Plasma obtained at the time of the blood culture was available for analysis by enzyme-linked immunosorbent assays for TNF and ILL Children who had positive blood cultures for Streptococcus pneumoniae were the cases. The controls were selected from children who had negative blood cultures. Results : During a 1-year period, 12 cases and 65 controls were identified. There was no significant difference in age, height or duration of fever, or illness acuity between the groups. The following were used as threshold values for a positive test: white blood cell (WBC) count >15.0 × 10⁹ cells/L, TNF >21.5 ng/mL, and IL1 >9.0 ng/mL. Using an estimated prior probability of bacteremia of 4%, the positive predictive value (PPV) and the negative predictive value (NPV) for bacteremia were 11.7% and 98.6% using the WBC count, 11.1% and 98.6% using the IL1 level, and 9.0% and 98.9% using the TNF level. The combination of WBC count with either TNF or IL1 gave an NPV of 100%, with PPVs of 8.5% for TNF and 9.9% for ILL Conclusions : Like the WBC count, TNF and IL1 are good negative but poor positive predictors of Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children. At present, the addition of plasma TNF or IL1 levels would add little to emergency physicians' ability to predict Streptococcus pneumoniae bacteremia. However, as the quantification of these cytokines becomes more rapid, available, and standardized, and more knowledge of TNF and IL1 levels during various illnesses is gained, their utility in the clinical setting for ruling out bacteremia should be further assessed.     

Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders

ABSTRACT: INTRODUCTION: The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship. METHODS: Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots. RESULTS: Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal. CONCLUSIONS: The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.     

失血增加内毒素血症危害性

目的　探索失血性休克加重内毒素血症对宿主危害的机理。方法　以新西兰大白兔为实验对象，动物从颈动脉放血至平均动脉压15.57±1.73kPa下降到6.13±0.267kPa，1h后将血液和等量生理盐水一同回输。8h后再经肠系膜血管按0.2mg/kg体重剂量注射大肠杆菌内毒素O     

Serum magnesium increases following severe hemorrhage in dogs blocked by verapamil treatment.

The opening of voltage sensitive calcium channels is an important event in the progression of irreversible shock, allowing the entry of toxic amounts of calcium (Ca2+) into the cells. Because intracellular magnesium (Mg2+) can efflux through these same channels, changes in serum Mg2+ may reflect the patency of these channels. In this study, electrolytes and selected serum enzymes were monitored in chronically instrumented conscious dogs to follow the progression of shock following a fixed volume hemorrhage. Plasma enzymes indicative of liver damage were elevated only in the terminal phase of hemorrhagic decompensation. A significant increase in serum Mg2+ was evident 60 min following hemorrhage, even though arterial pressure was still recovering. Serum Mg2+ continued to rise throughout the recovery and decompensating phases of shock. Verapamil treatment, which increased survival time and survival rate, significantly attenuated the changes in serum Mg2+ which normally followed hemorrhage. These results indicate that serum Mg2+ may be a useful indicator of the severity and the progression of hemorrhagic shock.     

复方丹参液对大鼠失血性休克合并凝血功能紊乱的治疗作用

为了观察大鼠失血性休克过程中凝血因子的变化及肝素、复方丹参注射液对凝血因子变化的影响,探讨复方丹参注射液对凝血功能紊乱的治疗作用,制作了失血性休克大鼠模型。将40只SD大鼠随机分为假手术组、休克组、复方丹参液组及肝素组,每组10只。检测各组休克后2、4、6小时血浆可溶性纤维蛋白单体复合物(SFMC)、血栓调节蛋白(TM)、抗凝血酶Ⅲ(ATⅢ)、D二聚体(DD)、组织型纤溶酶原激活剂(tPA)、纤溶酶原激活物抑制剂(PAI)变化及活化部分凝血活酶时间(APTT);比较肝素组与复方丹参液组出血并发症的发生率。研究结果表明:大鼠休克组血浆SFMC、DD水平明显高,于而ATⅢ明显低于其他3组(P<0.001),其他3组间比较,无显著性差异(P>0.05)。休克组、肝素组血浆TM水平明显增加(P<0.001),复方丹参组与假手术组间相比无显著性差异。休克组大鼠于休克2小时血浆tPA、DD水平明显升高,于休克4小时PAI达到高峰(P<0.001),而tPA水平有所下降。于休克6小时,血浆PAI水平下降,tPA继续降低,但PAI、DD尚维持于较高水平。肝素组血浆DD水平降低、tPA高于休克组、PAI无显著性不同。丹参组大鼠血浆tPA、PAI、DD均低于休克组,但均在正常范围内。休克组大鼠APTT进行性延长,至休克6小时达到高峰,平均59.7±11.86秒。肝素组APTT平均61.5±5.79秒     

Complement activation during hemorrhagic shock and resuscitation in swine

Activation of the complement (C) cascade is known to play a key role in the adverse immune consequences of hemorrhagic trauma with subsequent shock and resuscitation. However, it is not clear whether hypovolemia per se, without trauma and resuscitation, can also lead to C activation. To address this question, we studied the presence, kinetics, and cause of C activation in a porcine model of hemorrhagic shock and resuscitation in the absence of trauma. Pigs were bled to and kept at 35 mmHg for 90 min, followed by hypotensive resuscitation with different fluids and, finally, with shed blood. The animals developed severe lactic acidosis between 30 and 90 min, which was accompanied by a trend for initial rise and subsequent 40% drop of CH50/mL, indicating massive C activation even before resuscitation, i.e., before reperfusion damage could have occurred. Resuscitation with plasma expanders caused 20% additional C consumption, whereas whole blood raised CH50/mL. Plasma C5a decreased initially and then significantly increased at 60 and 180 min, whereas thromboxane B2 showed a 3-fold increase at 30 and 60 min. Plasma LPS was also increased above baseline at 90 and 180 min. In in vitro studies with pig blood, spontaneous C5a formation, as well as zymosan-induced C consumption, was significantly enhanced under the conditions of lactic acidosis. Our data suggest that lactic acidosis, endotoxemia, and possibly other ischemia-related tissue alterations act in a vicious cycle in inducing C activation and, hence, aggravation of shock. The biphasic course of CH50/mL and C5a changes may reflect yet unrecognized physiological responses to hemorrhage-related C activation.     

Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.

Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.     

Effect of anesthesia and surgery on plasma cytokine levels

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 μg/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 ±- 5.8 to 48.6 ±- 3.2 mm Hg, (mean ±- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin (P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration (P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock (P < .05) and 50-fold following endotoxin administration (P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels. Traumatic manipulation of the intestines sufficient to cause diffuse bowel injury and shock causes only small increases in plasma IL-6. Substantial increases in both TNF and IL-6 occur following a minimal endotoxin challenge showed an intact functional systemic response.     

Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock. Young, healthy baboons received either a sublethal dose of lipopolysaccharide (LPS) or an LD100 of live Escherichia coli bacteria, and one half of the animals in each group were continuously infused with IL-1 receptor antagonist (IL-1ra). Plasma IL-1 beta was not detected in this model of endotoxemia. Administration of IL-1ra had only minimal effects on the modest hemodynamic and metabolic responses to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In contrast, high circulating levels of IL-1 beta (range 300-800 pg/ml) were seen during lethal E. coli septic shock. IL-1ra treatment significantly attenuated the decrease in mean arterial blood pressure (MAP) (from -72 +/- 8 to -43 +/- 6 mm Hg; P less than 0.05) and cardiac output (from -0.81 +/- 0.17 to -0.48 +/- 0.15 liter/min; P less than 0.05), and significantly improved survival from 43 to 100% at 24 h (P less than 0.05). The plasma IL-1 beta and IL-6 responses to lethal E. coli septic shock were also significantly diminished by IL-1ra treatment (P less than 0.05), whereas tumor necrosis factor-alpha (TNF alpha) concentrations were unaffected. We conclude that an exaggerated systemic IL-1 beta response is characteristic of lethal E. coli septic shock, and contributes significantly to the hemodynamic and metabolic consequences of E. coli septic shock. IL-1ra can significantly attenuate the cytokine cascade and improve survival.