DETECTION OF CIRCULATING TUMOR NECROSIS FACTOR AFTER ENDOTOXIN ADMINISTRATION
DETECTION OF CIRCULATING TUMOR NECROSIS FACTOR AFTER ENDOTOXIN ADMINISTRATION
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DOI：
10.1056/nejm198806093182301
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发表时间：
1988-06-09
影响因子：
158.5
通讯作者：
WILMORE, DW
中科院分区：
文献类型：
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作者：
MICHIE, HR;MANOGUE, KR;WILMORE, DW
细胞因子，刺激的巨噬细胞的产物，被认为是介导许多宿主对细菌感染的反应，但增加的循环细胞因子浓度尚未在感染患者中检测到一致。我们测量了循环肿瘤坏死因子α（恶病质），白细胞介素-1 β，和γ-干扰素，以及生理和激素反应，在13名健康男性静脉注射大肠杆菌内毒素（4 ng/kg体重）后，并在对照期间的生理盐水管理。另外8名受试者在接受内毒素或生理盐水之前接受布洛芬。肿瘤坏死因子的血浆水平在整个对照期间通常低于35 μ g/ml，但在内毒素给药后90至180分钟增加至平均峰值浓度240 ± 100 μ g/ml。70 pg/ml，而35 ±.盐水给药后5 pg/ml。宿主反应与90分钟时循环肿瘤坏死因子的增加在时间上相关，症状的程度、白细胞计数的变化和促肾上腺皮质激素的产生与肿瘤坏死因子的峰值浓度在时间上相关。伊立替尼预处理不能阻止循环肿瘤坏死因子的升高（平均峰值血浆水平，170 ± 0.01）。70 μ g/ml），但在给予内毒素后大大减弱了症状和其它反应。循环白细胞介素-1 β的浓度而γ干扰素在内毒素给药后没有变化。我们的结论是，对内毒素的反应与循环肿瘤坏死因子的短暂脉冲有关，并且所产生的反应是通过环氧合酶途径实现的。
Cytokines, products of stimulated macrophages, are thought to mediate many host responses to bacterial infection, but increased circulating cytokine concentrations have not been detected consistently in infected patients. We measured plasma concentrations of circulating tumor necrosis factor alpha (cachectin), interleukin-1.beta., and gamma interferon, together with physiologic and hormonal responses, in 13 healthy men after intravenous administration of Escherichia coli endotoxin (4 ng per kilogram of body weight) and during a control period of saline administration. Eight additional subjects received ibuprofen before receiving endotoxin or saline. Plasma levels of tumor necrosis factor were generally less than 35 pg per milliliter throughout the control period, but increased 90 to 180 minutes after endotoxin administration to mean peak concentrations of 240 .+-. 70 pg per milliliter, as compared with 35 .+-. 5 pg per milliliter after saline administration. Host responses were temporally associated with the increase in circulating tumor necrosis factor at 90 minutes, and the extent of symptoms, changes in white-cell count, and production of ACTH were temporally related to the peak concentration of tumor necrosis factor. Ibuprofen pretreatment did not prevent the rise in circulating tumor necrosis factor (mean peak plasma level, 170 .+-. 70 pg per milliliter) but greatly attenuated the symptoms and other responses after endotoxin administration. Concentrations of circulating interleukin-1.beta. and gamma interferon did not change after endotoxin administration. We conclude that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.