Murphey E D, Traber D L
Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, USA.
Crit Care Med. 2000 Jun;28(6):2015-21. doi: 10.1097/00003246-200006000-00056.
Tumor necrosis factor (TNF)-alpha administration in large amounts can induce a state of shock similar to that seen during severe sepsis. The objective of this study was to determine whether small doses of TNF-alpha might decrease the disposition for the development of shock induced by a subsequent infusion of endotoxin and to determine whether the mechanism of this protective effect of TNF-alpha pretreatment could be associated with up-regulation of the anti-inflammatory cytokine interleukin (IL)-10.
Prospective, randomized, experimental study.
Investigative intensive care unit at an academic medical center.
A total of 14 female Yorkshire pigs, weighing 20-25 kg.
We studied two groups of animals-pigs treated with 500 ng/kg recombinant porcine TNF-alpha (n = 7) and pigs given diluent alone (n = 7). At 24 hrs after treatment, both groups of pigs were subjected to a 24-hr continuous infusion of lipopolysaccharide (LPS) at a rate of 80 ng/kg/min.
The mortality rate was determined in both groups. Hemodynamic indices, oxygen transport variables, total and differential white cell counts, and serum concentrations of TNF and IL-10 were determined at frequent intervals before and after TNF-alpha administration and during the LPS infusion. Additionally, peripheral blood mononuclear cells were collected for determination of messenger ribonucleic acid expression of IL-10 by reverse transcription-polymerase chain reaction. The administration of TNF-alpha at the dose used in this study did not have any profound effect. No pig treated with TNF-alpha died in response to the LPS infusion. In contrast, three of seven control pigs died during the LPS infusion. Lipopolysaccharide-induced arterial hypotension and arterial hypoxemia were attenuated in the TNF-alpha-treated group. Both groups had significant increases in serum concentrations of TNF-alpha in response to LPS, with no significant difference in peak serum TNF-alpha between groups. Neither serum concentrations of IL-10 nor expression of IL-10 messenger ribonucleic acid in circulating mononuclear cells differed between groups.
The administration of TNF-alpha attenuated the severity of hyperdynamic shock induced by a subsequent infusion of endotoxin. This effect could not be associated with increased expression or elaboration of the anti-inflammatory cytokine IL-10.
大量给予肿瘤坏死因子（TNF）-α可诱发一种类似于严重脓毒症时所见的休克状态。本研究的目的是确定小剂量TNF-α是否可能降低随后输注内毒素诱发休克的易感性，并确定TNF-α预处理这种保护作用的机制是否可能与抗炎细胞因子白细胞介素（IL）-10的上调有关。
前瞻性、随机、实验性研究。
一所学术医疗中心的研究重症监护病房。
共14只体重20 - 25千克的雌性约克夏猪。
我们研究了两组动物，一组用500纳克/千克重组猪TNF-α治疗的猪（n = 7）和另一组仅给予稀释剂的猪（n = 7）。治疗后24小时，两组猪均以80纳克/千克/分钟的速率接受24小时持续输注脂多糖（LPS）。
测定两组的死亡率。在给予TNF-α之前和之后以及LPS输注期间，频繁测定血流动力学指标、氧输送变量、白细胞总数和分类计数以及TNF和IL-10的血清浓度。此外，收集外周血单核细胞，通过逆转录-聚合酶链反应测定IL-10信使核糖核酸的表达。本研究中使用的剂量的TNF-α给药没有任何显著影响。接受TNF-α治疗的猪没有因LPS输注而死亡。相比之下，7只对照猪中有3只在LPS输注期间死亡。LPS诱导的动脉低血压和动脉低氧血症在TNF-α治疗组中有所减轻。两组对LPS反应时血清TNF-α浓度均显著升高，两组血清TNF-α峰值无显著差异。两组之间循环单核细胞中IL-10的血清浓度和IL-10信使核糖核酸的表达均无差异。
TNF-α给药减轻了随后输注内毒素诱发的高动力性休克的严重程度。这种作用与抗炎细胞因子IL-10表达增加或分泌增多无关。
