清除循环肿瘤坏死因子对急性损伤的影响

目的 研究亲和免疫吸附清除循环肿瘤坏死因子（ＴＮＦ）对内毒素性急性肺损伤动物的保护作用。方法 以６１只新西兰兔为实验动物，建立内毒素急性肺损伤模型，随机分为三组：（１）免疫吸附组（２７只）颈静脉注射自制脂多糖（ＬＰＳ）１００×１０＾８ｃｕｆ．ｋｇ＾－１小时开始血液灌流，通过含重组肿瘤坏死因子α（ｒＨｕＴＮＦ－α）单克隆抗体的吸附柱，灌流时间２小时；（２）致伤组（２７只）颈静脉注射ＬＰＳ，无吸附柱，     

脂多糖致肺血管内巨噬细胞形态和功能的改变

目的探讨肺血管内巨噬细胞（ＰＩＭ）在感染性急性肺损伤（ＡＬＩ）发病中的作用。方法仿Ｍｏｒｔｏｎ法灌洗肺血管床，贴壁法分离猪ＰＩＭ，并用光镜、电镜观察鉴定；胸腺细胞增殖法测脂多糖（ＬＰＳ）刺激前后ＰＩＭ培养上清白细胞介素１β（ＩＬ－１β）活性，酶联免疫吸附试验（ＥＬＩＳＡ）法测肿瘤坏死因子α（ＴＮＦ－α）、白细胞介素６（ＩＬ－６）、白细胞介素８（ＩＬ－８）含量。结果刺激后的ＰＩＭ伪足增长、增多，溶酶体和吞噬体亦增多；释放ＴＮＦα、ＩＬ－１β、ＩＬ－６、ＩＬ－８增多，峰值分别出现在刺激后的１ｈ、２ｈ、４ｈ和６ｈ。与刺激前相比，Ｐ＜０．０１。结论改良的Ｍｏｒｔｏｎ法能成功分离猪ＰＩＭ；ＬＰＳ刺激后的ＰＩＭ吞噬分泌功能活跃，其中ＴＮＦα、ＩＬ－１β升高最早，提示其在ＡＬＩ发病早期起重要作用；而ＩＬ－６、ＩＬ－８升高较晚，可能在ＡＬＩ发病后期起重要作用     

口服乳果糖对肝脏病患者血清内毒素和细胞因子的影响

目的：观察乳果糖治疗对急、慢性肝病患者血清内毒素、细胞因子水平及肝功能指标的影响。方法：在８９例急、慢 性肝炎、肝硬化患者中,４９例口服乳果糖２０日,检测两次血清内毒素、细胞因子、胆红素及转氨酶。结果：治疗前,３组 患者血清内毒素水平有差异,肝硬化患者最高（６９．３ｐｇ／ｍｌ± ２３．６ｐｇ／ｍｌ）,慢性肝炎患者最低 （２．４ｐｇ／ｍｌ± ７．９ｐｇ／ｍｌ）,内毒素与ＴＮＦ－α（ｒ＝０．５５５,Ｐ＜０．０１）、ＩＬ－６（ｒ＝０．５３１,Ｐ＜０．０１）、ＩＬ－８（ｒ＝０．４４０,Ｐ＜０．０５）、Ｇ－ＣＳＦ（ｒ＝０.４４ ０,Ｐ＜０．０５）呈正相关,口服乳果糖组血清内毒素,ＴＮＦ－α、ＩＬ－６、ＩＬ－８和Ｇ－ＣＳＦ水平下降及肝功能改善较未服药者明 显。结论：急、慢性肝病时内毒素可能是ＴＮＦ－α、ＩＬ－６、ＩＬ－８和Ｇ－ＣＳＦ的诱导物,其共同参与肝脏炎症反应。口服乳果糖 可能通过降低血清内毒素、细胞因子水平而对肝病患者有利。     

内毒素／肿瘤坏死因子所致肝细胞损害机制的体外研究

为了解内毒素（ＬＰＳ）／肿瘤坏死因子（ＴＮＦ）所致肝细胞损害的机制，以乳酸脱氢酶（ＬＤＨ）及噻唑蓝染色（ＭＴＴ）为细胞毒性指标，利用Ｗｉｓｔａｒ大鼠肝细胞进行了ＬＰＳ及其介质ＴＮＦ等的肝细胞损害机制研究。结果发现：ＬＰＳ、ＴＮＦ－α、ＩＬ－１、ＩＬ－６等对肝细胞ＬＤＨ漏出及ＭＴＴ无显著影响（Ｐ＞０．０５），仅在ＬＰＳ、ＬＰＳ／ＴＮＦ－α加入肝细胞－Ｋｕｐｆｆｅｒ细胞混合培养组后有所变化；经ＧａｌＮ／ＬＰＳ体内作用后分离的Ｋｕｐｆｆｅｒ细胞与正常肝细胞混合培养，加入ＬＰＳ、ＴＮＦ及ＬＰＳ／ＴＮＦ－α均可致ＬＤＨ漏出显著增高（Ｐ＜０．０ｌ），多粘菌素Ｂ及抗－ＴＮＦ能分别完全和部分阻断此效应；经ＬＰＳ或ＴＮＦ－α体内作用后抽取的大鼠血清，加入培养肝细胞可致ＬＤＨ漏出显著增高（Ｐ＜０．０１）与ＭＴＴ显著降低（Ｐ＜０．０５），经５６℃灭活后此细胞毒性作用完全消失。上述结果提示，ＬＰＳ及其介质ＴＮＦ无肝细胞直接毒性作用，而经其活化的Ｋｕｐｆｆｅｒ细胞可能引起一系列瀑布效应，导致肝细胞损害。     

间质性肺疾病支气管肺泡灌洗液中性粒细胞趋化因子和肿瘤坏死因子水平及其临床意义

目的探讨间质性肺疾病（ＩＬＤ）时中性粒细胞趋化因子（ＮＣＦ）和肿瘤坏死因子（ＴＮＦα）与ＩＬＤ活动性的关系。方法用膜滤过和放射免疫法检测１１例结节病、７例特发性肺间质纤维化（ＩＰＦ）患者和８名健康者血清及支气管肺泡灌洗液（ＢＡＬＦ）中ＮＣＦ活性及ＴＮＦα水平。结果７例ＩＰＦ患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα分别为２０３±４４ｃｅｌｓ／１０ＨＰ、１１７±２９ｎｇ／Ｌ，明显高于８名对照组（８３±４５ｃｅｌｓ／１０ＨＰ、６５±１４ｎｇ／Ｌ、Ｐ＜０．０１）；１１例结节病患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα分别为１８６±５０ｃｅｌｓ／１０ＨＰ、１２±３ｎｇ／Ｌ，明显高于８名对照组（Ｐ＜０．０１）。ＩＰＦ组ＢＡＬＦ中ＮＣＦ、ＴＮＦα均与中性粒细胞百分比呈正相关（ＮＣＦ：ｒ＝０．８９，Ｐ＜０．０１，ＴＮＦα：ｒ＝０．８６，Ｐ＜０．０５），结节病组ＢＡＬＦ中ＮＣＦ、ＴＮＦα均与淋巴细胞百分比呈正相关（ＮＣＦ：ｒ＝０．７８，Ｐ＜０．０１；ＴＮＦα：ｒ＝０．７３，Ｐ＜０．０１）。结论ＩＰＦ和结节病患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα水平可做为肺泡炎活动性的标志     

幽门螺杆菌感染患者白细胞介素—8和肿瘤坏死因子—α的表达

为研究幽门螺杆菌（Ｈｐ）感染时血清及胃粘膜组织白细胞介素（ＩＬ）－８、肿瘤坏死因子（ＴＮＦ）－α水平及其病理作用，采用放射免疫法和酶联免疫吸附试验夹心法分别检测了Ｈｐ（－）～（＋＋＋）者血清和胃粘膜组织中的ＩＬ－８、ＴＮＦ－α，并观察胃粘膜组织炎症活动程度与Ｈｐ感染密度的关系。结果：（１）胃粘膜组织ＩＬ－８、ＴＮＦ－α水平高低依次为Ｈｐ感染（＋＋＋）＞（＋＋）＞（＋）＞对照组，４组间差异均有显著意义（Ｐ＜０．０５）。（２）Ｈｐ根除后血清ＩＬ－８水平无明显变化，ＴＮＦ－α水平则明显下降；胃粘膜组织ＩＬ－８、ＴＮＦ－α水平下降，与根除前相比有显著性差异（Ｐ＜０．０５）。（３）胃粘膜组织炎症活动程度与Ｈｐ感染密度相关（精确概率值为０．００２６，Ｐ＜０．０１）。结果提示：Ｈｐ感染时胃粘膜组织ＩＬ－８、ＴＮＦ－α水平明显高于对照组，损伤程度随Ｈｐ感染密度增加而加重     

白细胞抑制因子对鼠急性肺损伤时白细胞的影响

为探讨白细胞抑制因子（ＮＩＦ） 转基因后在鼠急性肺损伤时肺内、循环静脉血中白细胞的影响。本实验采用阳离子脂类,ＮＩＦ基因重组法,用脂多糖（ＬＰＳ） 致鼠急性肺损伤,分组测定静脉血及肺泡内白细胞的变化。结果发现ＬＰＳ诱发急性肺损伤后２ｈ 静脉血中白细胞明显减少（ Ｐ＜ ０－０１） ,在肺泡灌洗液内中性粒细胞明显增多（ Ｐ＜ ０－０１） 。而采用ＮＩＦ／ＬＰＳ注射组的肺泡灌洗液内中性粒细胞数与ＬＰＳ组比较却明显降低（ Ｐ＜ ０－０５） 。在ＮＩＦ注射组中单核细胞明显增多。ＮＩＦ转基因后,对ＬＰＳ诱发的急性肺损伤中白细胞浸润及肺内聚集现象有明显的抑制作用。ＮＩＦ注射后对白细胞总数无明显影响,可使单核细胞数量增加,这可能是机体免疫反应的结果。     

哮喘气道炎症粘附机制的实验研究

目的评价细胞间粘附分子１（ＩＣＡＭ１）、Ｐ选择素在哮喘气道炎症粘附机制中的作用,进一步阐明哮喘的发病机理。方法用酶联免疫吸附试验、肺组织免疫组化检查和呼吸生理学方法系统观察正常组和哮喘组豚鼠各项指标。结果（１）哮喘组豚鼠肺潮气量、动态肺顺应性（Ｃｄｙｎ）和肺气道阻力与对照组比较差异有显著性（Ｐ＜０．０１及Ｐ＜０．０５）。（２）哮喘组豚鼠血浆和肺泡灌洗液（ＢＡＬＦ）可溶性ＩＣＡＭ１（ｓＩＣＡＭ１）、可溶性Ｐ选择素、血清和ＢＡＬＦ嗜酸粒细胞阳离子蛋白（ＥＣＰ）与对照组比较,差异有显著性（Ｐ＜０．０１）;ＢＡＬＦ中白细胞介素８（ＩＬ８）与对照组比较差异也有显著性（Ｐ＜０．０１）。（３）哮喘组豚鼠肺组织（气道上皮和血管内皮）ＩＣＡＭ１和ＩＬ８表达与对照组比较,差异有显著性（Ｐ＜０．０１）。结论ＩＣＡＭ１、Ｐ选择素、ＩＬ８、ＥＣＰ参与介导了哮喘气道炎症的粘附过程     

血清IL-2和TNF水平检测对口腔颌面部肿瘤患者的临床价值探讨

对３２例口腔颌面部良性肿瘤、２５例恶性肿瘤手术前后患者及２０例正常对照者进行了血清白细胞介素２（ＩＬ－２）及肿瘤坏死因子（ＴＮＦ）水平检测。结果发现，良性肿瘤组ＩＬ－２、ＴＮＦ水平与对照组无显著性差异（Ｐ〉０．０５）；恶性肿瘤组ＩＬ－２水平与对照组有显著性差异（Ｐ〈０．０１）。血清ＩＬ－２水平与临床分期有关，手术前后差异显著（Ｐ〈０．０１），而ＴＮＦ水平与对照组无差异，手术前后也无明显变化。表明血     

胸腺肽α1治疗重症肝炎的免疫调节研究

为了解日达仙的免疫调节作用,选取１８例下肝炎病人用日达仙（Ｔα１）治疗,并在治疗前后检测内毒素（ＬＳＰ）、肝瘤坏死因子（ＴＮＦ）、白细胞介素２受体（ＩＬ－２Ｒ）、白细胞介素４（ＩＬ－４）、白细胞介素６（ＩＬ－６）、及Ｔ细胞亚群（ＣＤ８＾＋、ＣＤ４＾＋）。结果治疗前ＬＳＰ、ＴＮＦ、ＩＬ－２Ｒ、ＩＬ－６、ＣＤ８＾＋均增高９Ｐ〈０．０１）,而ＩＬ－４及ＣＤ４＾＋降低。经Ｔα１治疗后ＬＳＰ、ＴＦ、ＩＬ－２     

Experimental study of Tong Xia purgative method in ameliorating lung injury in acute necrotizing pancreatitis

AIM To investigate the role of tumor necrosis factor (TNF) in lung injury during acute necrotizing pancreatitis (ANP ), and the therapeutic effect of "Tong Xia" purgative method in minimizing the severity of lung injury.METHODS Fourteen canines were randomly divided into 3 groups: the "Tong Xia" treatment group ( n = 5) using Dachengqitang; saline control group (n = 5), and the sham operation group (n= 4). TNF activity in serum and in bronchoalveolar lavage fluid (BALF), the serum endotoxin levels were measured, and the severity of lung injury evaluated.RESULTS Elevation of TNF activity was more prominent in BALF than in serum. TNF activity in serum at 6 and 12 hours and in BALF was significantly decreased in the "Tong Xia"treatment group than in the saline control one (q=21.11, q=12.07, q=9.03, respectively, P＜0.01) and the lung injury was significantly alleviated at 12 hours as compared with that in the saline group, manifested as amelioration of the lung wet/ dry weight ratio, decrease in protein concentration and neutrophils count in BALF, and improvement of pulmonary inflammatory changes. A positive correlation was demonstrated between serum TNF activity and endotoxin level.CONCLUSIONHypersecretion of TNF is shown to be one of the major causes of lung injury during ANP;"Tong Xia"purgative method could alleviate the degree of Iung injury mediated by TNF.     

Effect of catalase on endotoxin-induced acute lung injury in unanesthetized sheep

Administration of endotoxin intravenously to unanesthetized sheep causes an acute lung injury characterized by increased microvascular barrier permeability and subsequent pulmonary edema. Endotoxin-induced sheep lung injury can be attenuated by leukocyte depletion, and may be mediated by toxic metabolites of oxygen. We studied effects of administering catalase, which catalyzes conversion of hydrogen peroxide to oxygen and water, to sheep subsequently infused with endotoxin to test the hypothesis that hydrogen peroxide plays a role in the pathogenesis of lung injury. We found that infusions of endotoxin (1 microgram/kg) into untreated sheep caused the expected biphasic response, a transient, early, marked pulmonary arterial hypertension followed by a prolonged increase in protein-rich lung lymph flow characteristic of increased microvascular permeability filtration in the lungs. Intraperitoneal injections of catalase (50 mg/kg) prior to infusing endotoxin in these same sheep resulted in substantial catalase activity in plasma and in lung lymph, and attenuated the expected changes in pulmonary arterial pressure, lung lymph flow, and arterial leukocyte counts and oxygen tension after endotoxin infusions. Furthermore, mechanical elevation of hydrostatic pressure in the lungs of a catalase-treated sheep infused with endotoxin resulted in increased lung lymph flow with a decreased protein concentration, indicating that the microvascular barrier to fluid and protein was functionally intact. Administration of catalase that was inactivated by reaction with hydrogen peroxide in the presence of aminotriazole or administration of the catalase vehicle, thymol, had no effects on the sheep responses to endotoxin. We conclude that hydrogen peroxide plays a role in the pathogenesis of endotoxin-induced acute lung injury in sheep.     

Manipulations of core temperatures in ischemia-reperfusion lung injury in rabbits

The present study was designed to determine the effect of various core temperatures on acute lung injury induced by ischemia-reperfusion (I/R) in our isolated rabbit lung model. Typical acute lung injury was successfully induced by 30 min of ischemia followed by 90 min of reperfusion observation. The I/R elicited a significant increase in pulmonary arterial pressure, microvascular permeability (measured by using the capillary filtration coefficient, Kfc), Delta Kfc ratio, lung weight gain and the protein concentration of the bronchoalveolar lavage fluid. Mild hypothermia significantly attenuated acute lung injury induced by I/R, all parameters having decreased significantly (p<0.05); conversely, mild hyperthermia did not further exacerbate acute lung injury. These experimental data suggest that mild hypothermia significantly ameliorated acute lung injury induced by ischemia-reperfusion in rabbits.     

Changes and significance of chemiluminescence of polymorphonuclear leukocytes in endotoxin-induced lung injury in conscious sheep]

The chemiluminescence (CL) of polymorphonuclear leukocytes and its relation with pulmonary microvascular permeability after endotoxin-induced lung injury in conscious sheep with lung lymph fistula were observed. Four hours after the injury the CL of PMNs increased from 0.27 cpm/PMN of baseline to 0.69 cpm/PMN (P < 0.05). The increment of the CL had positive correlation with the increment of lung lymph flow or permeability index (r = 0.632 0.638 P < 0.05), suggesting that the increase of pulmonary microvascular permeability after the endotoxin injury had relation with the increase of the respiratory tract of PMNs.     

The role of cytokine-induced neutrophil chemoattractant-1 in neutrophil-mediated remote lung injury after intestinal ischaemia/reperfusion in rats

OBJECTIVE: Remote lung injury is induced by ischaemia/reperfusion (I/R) of the gastrointestinal tract and the liver following hypovolaemic shock. In the present study, the role of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin (IL)-8 family, in neutrophil-mediated remote lung injury following intestinal I/R was investigated in anaesthetized rats. METHODOLOGY: The I/R group was subjected to 60 min of occlusion of the superior mesenteric artery with laparotomy, followed by 240 min of intestinal reperfusion. The sham-operated (sham) group was subjected to the same procedures with the exception of intestinal I/R. RESULTS: In the I/R group, the permeability index of the lung, the neutrophil count in pulmonary vascular lavage fluid and bronchoalveolar lavage fluid (BALF), lung myeloperoxidase activity and neutrophil oxidative production were all significantly greater than those in the sham group. Cytokine-induced neutrophil chemoattractant-1 levels in blood and BALF were significantly increased at 240 min after intestinal reperfusion. There was a significant relationship between neutrophils in BALF and CINC-1 level in BALE CONCLUSION: These findings suggest that intestinal reperfusion was associated with activation and accumulation of neutrophils in the lung and resulted in remote lung injury with increased microvascular permeability. Thus, CINC-1 in BALF may induce neutrophil migration from the pulmonary vessels to the interstitium and alveolar spaces in remote lung injury after intestinal I/R.     

Dibutyryl-cAMP blocks endotoxin-induced lung injury in rats

We investigated the effect of dibutyryl-cAMP pretreatment on endotoxin-induced hemodynamic changes and lung vascular injury in rats. In catheter-implanted, unanesthetized rats, intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) decreased cardiac output and systemic blood pressure while increasing total pulmonary vascular resistance. Db-cAMP (1 mg given intraperitoneally every 30 min), although not significantly affecting cardiac output and systemic blood pressure, blocked the increase in total pulmonary resistance caused by endotoxin. Ninety minutes after intraperitoneal endotoxin injection, perfused lungs from endotoxin-treated rats exhibited increased pulmonary vascular permeability, as assessed by increased extravascular accumulation of 125I-albumin and water. Db-cAMP treatment in vivo markedly attenuated the increases in lung albumin leak index and wet-to-dry weight ratio caused by endotoxin without affecting lung microvascular pressures. This protective action of db-cAMP is not due to its effect on prostaglandin or leukotriene synthesis since endotoxin-stimulated increases in lung tissue 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotriene C4 were not inhibited. We conclude that db-cAMP blocks endotoxin-induced lung injury in the rat by a mechanism independent of eicosanoid products and speculate that agents that increase intracellular cAMP may be therapeutically useful in acute lung vascular injury.     

乙酰化白藜芦醇对脂多糖诱导急性肺损伤中微循环修复作用机制探究

目的观察脂多糖(LPS)诱导急性肺损伤大鼠肺组织中微循环的变化,探讨乙酰化白藜芦醇对其干预作用及机制。方法 32只SD大鼠随机分为空白对照组、LPS处理组、乙酰化白藜芦醇预处理组和白藜芦醇预处理组,每组8只。采用气管内滴注LPS(5 mg/kg)的方法制作急性肺损伤动物模型,观察病理变化、肺组织湿/干重比值,用伊文思蓝法检测肺微血管通透性,用酶联免疫吸附试验法检测肺组织中肿瘤坏死因子α和白细胞介素1β的含量,用蛋白质印迹法检测细胞骨架重构相关蛋白FAK、cofilin的表达变化,免疫荧光观察肺微血管内皮细胞单层细胞间隙改变情况。结果 LPS干预4 h后,大鼠肺部损伤明显,肿瘤坏死因子α和白细胞介素1β的含量增高,肺湿/干重比值及通透性明显增加,FAK-cofilin通路明显激活,肺微血管内皮单层细胞间隙明显增加;乙酰化白藜芦醇预处理显著减轻了LPS导致的急性肺损伤,减少了炎症因子的释放,并且抑制了FAK-cofilin通路的激活及肺微血管内皮单层细胞间隙的增加。结论肺微循环的改变参与了LPS诱导肺损伤的发生发展,乙酰化白藜芦醇能够通过抑制FAK-cofilin通路减轻肺损伤。     

Lung-marginated monocytes modulate pulmonary microvascular injury during early endotoxemia

RATIONALE: The role of monocytes in acute endotoxemia has been ascribed to systemic release of mediators within the central circulation. Little is known about the potential role of "marginated" monocytes in regulating microvascular inflammatory signaling. OBJECTIVES: To investigate whether lung-marginated monocytes can locally activate pulmonary endothelial cells through cell contact-dependent interactions in early endotoxemia. METHODS: Mice were challenged with LPS to produce acute endotoxemia and pulmonary vascular injury. Adoptive transfer of ex vivo LPS-stimulated donor leukocytes to recipient mice was also performed to evaluate cell-associated inflammatory signaling between monocytes and endothelial cells within the lung. Cell suspensions from excised lungs were analyzed by flow cytometry for expression of tumor necrosis factor alpha (TNF-alpha) on monocytes and cell adhesion molecules on endothelial cells. RESULTS: Substantial numbers of monocytes rapidly marginated to the lungs after endotoxin challenge in mice, and lung-marginated monocytes expressed significantly higher levels of membrane TNF than circulating monocytes, due to higher TNF production by the marginated cells. Injection of activated wild-type donor leukocytes to wild-type or TNF receptor double knockout recipients demonstrated that lung-marginated monocytes can induce TNF-dependent upregulation of adhesion molecules on pulmonary endothelial cells. Injection of activated donor leukocytes from TNF knock-in mice that express uncleavable mutant membrane TNF also induced adhesion molecule upregulation in wild-type recipients without a systemic soluble TNF release. CONCLUSIONS: These results reveal a previously unacknowledged role for lung-marginated monocytes in early endotoxemia, exerting local, cell-associated TNF signaling within the pulmonary microcirculation, contributing to the evolution of pulmonary vascular injury.     

TNF- and LPS-induced changes of lung vascular permeability: studies in unanesthetised sheep

There have been reports that the administration of TNF produces many of the cardiopulmonary changes seen with endotoxin (LPS). We asked whether all of LPS effects can be mimicked by TNF infusion. The effects of infusion of (human recombinant) TNF (50 micrograms/kg/30 min) and LPS (3 micrograms/kg/30 min) on permeability characteristics of sheep lungs were compared. Thirteen sheep were chronically instrumented for cardiopulmonary studies including lung lymph data. Infusion of LPS and TNF result in an increase of body temperature and lung lymph protein clearance (measured as the product of Lymph Flow and Lymph/Plasma Protein Ratio). The two responses had entirely different time courses. This might be related to the significantly longer period of pulmonary hypertension (MPAP) with LPS, which was only transient with TNF. Similar differences in plasma levels of thromboxane B2 (TxB2) were also noted. There were also differences in leukocyte kinetics, arterial blood gases, and plasma lactate levels. This indicates that although TNF infusion results in an increased pulmonary microvascular permeability, this event occurs without concomitant changes in thromboxane metabolism and exhibits time characteristics somewhat different from endotoxin.