Koch T, Heller S, Weber K, Heller A, Urbaschek R
Institut für Anästhesiologie und Operative Intensivmedizin.
Anasthesiol Intensivmed Notfallmed Schmerzther. 1997 Jul;32(7):420-5. doi: 10.1055/s-2007-995083.
The therapeutic impact of intravenous immunoglobulins (ivIG) in septic patients remains controversial. Until now, the mechanisms of action have not been fully elucidated. Since polymorphonuclear neutrophils (PMN) play a key role in host defence, this study focuses on the effects of ivIG on bacterial clearance and PMN respiratory burst activity during endotoxinaemia. For this purpose, it was investigated whether ivIG improves blood clearance and organ colonisation as well as PMN functions after experimentally induced bacteraemia in rabbits.
The experiments were performed in 30 anaesthetised rabbits. To determine quantification of bacterial killing in vivo, defined numbers of exogenous Escherichia (E.) coli 1.3 x 10(8) CFU) were injected intravenously in untreated animals (n = 10) or 60 min after infusion of endotoxin (LPS: 40 micrograms/kg/h) in groups without (n = 10), and after pretreatment with ivIG (Sandoglobulin, 0.5 g/kg body weight, n = 10), respectively. Parameters monitored were rates of bacterial elimination from the blood, LPS clearance, arterial pressure, blood gases and white blood cell counts, PMN burst activity was determined using a flow cytometry assay. Samples of liver, kidney, spleen and lung were collected for bacterial counts 180 min following E. coli injection.
Compared to controls, endotoxinaemia resulted in a prolonged elimination of the injected E. coli out of the blood associated with a significantly (p < 0.01) higher colonisation of all organs. Pretreatment with ivIG improved LPS clearance and significantly reduced bacterial colonisation of lung and kidney (p < 0.01). This was paralleled by an enhanced PMN respiratory burst activity compared to untreated animals (p < 0.05).
The reduced bacterial colonisation of lung and kidney in correlation with an increased PMN bactericidal activity in endotoxinaemia suggest an improved granulocyte-dependent bacterial killing due to ivIG application.
静脉注射免疫球蛋白（ivIG）对脓毒症患者的治疗效果仍存在争议。迄今为止，其作用机制尚未完全阐明。由于多形核中性粒细胞（PMN）在宿主防御中起关键作用，本研究聚焦于ivIG对内毒素血症期间细菌清除及PMN呼吸爆发活性的影响。为此，研究了ivIG在实验性诱导兔菌血症后是否能改善血液清除、器官定植以及PMN功能。
实验在30只麻醉兔身上进行。为测定体内细菌杀灭的定量情况，在未治疗的动物（n = 10）中静脉注射确定数量的外源性大肠杆菌（1.3×10⁸CFU），或在未注射内毒素（LPS：40微克/千克/小时）的组（n = 10）以及用ivIG预处理（Sandoglobulin，0.5克/千克体重，n = 10）的组中，于注射内毒素60分钟后静脉注射相同数量的大肠杆菌。监测的参数包括血液中细菌清除率、LPS清除率、动脉血压、血气和白细胞计数，使用流式细胞术测定PMN爆发活性。在注射大肠杆菌180分钟后，采集肝脏、肾脏、脾脏和肺的样本进行细菌计数。
与对照组相比，内毒素血症导致注入血液中的大肠杆菌清除时间延长，且所有器官的定植显著增加（p < 0.01）。用ivIG预处理可改善LPS清除率，并显著降低肺和肾脏的细菌定植（p < 0.01）。与未治疗的动物相比，这伴随着PMN呼吸爆发活性增强（p < 0.05）。
内毒素血症时肺和肾脏细菌定植减少，同时PMN杀菌活性增加，提示应用ivIG可改善粒细胞依赖性细菌杀灭作用。
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