Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines.
Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines.
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正常人类受试者体内施用脂多糖（LPS）后的外周血白细胞动力学。
DOI：
10.1097/00000658-198908000-00018
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发表时间：
1989
影响因子：
9
通讯作者：
Calvano,SE
中科院分区：
文献类型：
--
作者：
Richardson,RP;Rhyne,CD;Fong,Y;Hesse,DG;Tracey,KJ;Marano,MA;Lowry,SF;Antonacci,AC;Calvano,SE
脂多糖(脂多糖，内毒素)可引起血浆恶病质/肿瘤坏死因子、肾上腺素和皮质醇的显著升高。这项研究考察了正常人注射内毒素后血白细胞亚群和血浆介质变化之间的时间关系。12名健康志愿者静脉滴注纯化的内毒素(20U/kg大肠杆菌)5min。在输注后不同的时间间隔采集血样，用流式显微荧光法分析不同的细胞计数和淋巴细胞亚群(CD2、CD3、CD4、CD8、CD20和人类白细胞抗原DR)，并测定血浆恶病质/肿瘤坏死因子、肾上腺素和皮质醇。血浆cachcctin/TNF在注药后75分钟和90分钟显著升高，注药后75分钟血浆cachcctin/TNF峰值为261±115pg/ml。血浆肾上腺素在注药后1小时显著升高，达181+/-75 pg/ml，皮质醇在注药后1~5小时显著升高，注药后3小时达34+/-3[mU]g/dl。输液后1小时出现严重的单核细胞减少症(P<；0.01)。与血浆皮质醇升高相关的是早期粒细胞减少逆转为显著的粒细胞减少(与输注前相比P<；0.01)，而在输注后1至6小时观察到明显的淋巴细胞减少(P<；0.01)。在高皮质醇血症期间，CD2、CD3和CD4淋巴细胞百分比降低(P<0.01)，CD20和HLA-DR淋巴细胞百分比升高(P<0.01)。CD8淋巴细胞在输注后1~24小时略有下降(P<；0.01)，但相对于1小时的最低点，在血浆皮质醇浓度升高期间，CD8淋巴细胞的百分比显著上升。6名健康志愿者注射肾上腺素(30 ng/kg/min)6小时后，出现单核细胞增多症(P<；0.05)和粒细胞增多症(P<；0.01)，而淋巴细胞数量和淋巴细胞亚群百分比没有变化。以往的报道表明，在体内输注糖皮质激素会导致明显的粒细胞减少、单核细胞减少和淋巴细胞减少，CD3和CD4淋巴细胞的百分比下降。本研究中记录的外周血白细胞动力学与体内应用皮质类固醇后观察到的模式相似。这项研究表明，急性肾上腺皮质对内毒素血症的反应主要介导了随后白细胞亚群的变化。
Lipopolysaccharide (LPS, endotoxin) administration to human subjects elicits significant elevations in plasma cachectin/TNF, epinephrine, and cortisol. This study examined the temporal relationship between changes in blood leukocyte subsets and plasma mediators following endotoxin administration to normal human subjects. A five-minute intravenous infusion of purified LPS (20 units/kg Escherichia coli) was administered to 12 healthy volunteers. Blood samples were obtained at varying intervals after infusion and analyzed for differential cell counts and lymphocyte subsets (CD2, CD3, CD4, CD8, CD20, and HLA-DR) by flow microfluorimetry, and also assayed for plasma cachectin/TNF, epinephrine, and cortisol. Plasma cachcctin/TNF was significantly elevated at 75 and 90 minutes after infusion with a peak concentration of 261+/-115 pg/ml noted 75 minutes after infusion. A significant plasma epinephrine elevation of 181+/-75 pg/ml was demonstrated one hour after infusion, while significant elevations in plasma cortisol were noted from one to five hours after infusion with a peak level of 34+/-3 [mu] g/dl three hours after infusion. A profound monocytopenia (p< 0.01) was noted one hour after infusion. Temporally associated with the rise in plasma cortisol was a reversal of the early granulocytopenia to a significant granulocytosis (p< 0.01 versus preinfusion mean), whereas a marked lymphocytopenia (p< 0.01) was observed from one to six hours after infusion. During the period of hypercortisolemia, CD2, CD3, and CD4 lymphocyte percentages were decreased (p< 0.01) while CD20 and HLA-DR lymphocyte percentages were increased (p< 0.01). There was a small percentage decrease in CD8 lymphocytes from one to 24 hours after infusion (p< 0.01), although relative to the one-hour nadir, there was a significant rise in the percentage during the time of elevated plasma cortisol concentrations. A six-hour infusion of epinephrine (30 ng/kg/min) administered to six healthy volunteers resulted in a monocytosis (p< 0.05) and granulocytosis (p< 0.01) without a change in lymphocyte number or lymphocyte subset percentage. Previous reports have shown that in vivo corticosteroid infusion causes a prominent granulocytosis, monocytopenia, and lymphocytopenia with a decrease in the percentages of CD3 and CD4 lymphocytes. The peripheral blood leukocyte dynamics documented in the current study are similar to patterns observed following in vivo corticosteroid administration. This study suggests that the acute adrenocortical response to endotoxemia primarily mediates the subsequent changes in leukocyte subsets.