Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia
Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia
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DOI：
10.1172/jci118469
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发表时间：
1996-02-01
影响因子：
15.9
通讯作者：
Lowry, SF
中科院分区：
文献类型：
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作者：
vanderPoll, T;Coyle, SM;Lowry, SF
为评价不同时间注射肾上腺素对体内内毒素反应的影响，进行了以下实验：(A)8名受试者在注射肾上腺素(30 ng/kg/min)后4-24小时采集的血液在脂多糖刺激后产生的肿瘤坏死因子比开始输注前的血液要少。和(B)17名健康男性接受肾上腺素的持续输注(每分钟30 ng/kg)，开始时间为3小时(EPI-3；N=5)或注射前24 h(EPI-24；n=6)或静脉注射生理盐水(n=6)后(2 ng/kg，批次EC-5)。EPI-3抑制脂多糖诱导的体内肿瘤坏死因子的产生，并促进IL-10的释放(P<0.005)，而EPI-24仅抑制肿瘤坏死因子的分泌(P=0.05)。在单独的全血体外实验中，肾上腺素通过对α和β肾上腺素能受体的联合作用，增加了内毒素诱导的IL-10的释放。此外，在脂多糖刺激的血液中，肾上腺素引起的IL-10水平的增加仅对同时抑制肿瘤坏死因子的产生起到微乎其微的作用。肾上腺素，无论是内源性产生的，还是作为脓毒症治疗的一个组成部分，在全身感染过程的早期，可能对细胞因子网络具有净抗炎作用。
Short-term preexposure of mononuclear cells to epinephrine inhibits LPS-induced production of TNF, whereas preexposure for 24 h results in increased TNF production, To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: (a) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and (b) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n = 5) or 24 h (EPI-24; n = 6) before LPS injection or an infusion of normal saline (LPS; n = 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P < 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion (P = 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on alpha and beta adrenergic receptors. Further, in LPS-stimulated blood, the increase in IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection.