Department of Neonatology, University of Heidelberg, Medical School, Heidelberg, Germany.
Neonatology. 2011;99(2):140-5. doi: 10.1159/000313967. Epub 2010 Aug 27.
Sepsis continues to be a leading cause of morbidity and mortality in newborns.
As both nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) appear to be critical mediators in inflammatory response, we studied the effects of lipopolysaccharide (LPS) on expression and function of NF-κB and p38 MAPK in whole neonatal cord and adult blood.
Th1/Th2 cytokine concentrations and phosphorylation of NF-κB and p38 MAPK were determined by flow-cytometric analysis.
Tumor necrosis factor-alpha (TNF-α), IL-6, and IL-10 concentrations were significantly elevated in supernatants of neonatal and adult blood after LPS stimulation for 4 h. IFN-γ, IL-4, and IL-2 showed no significant alterations. Furthermore, TNF-α concentrations were significantly higher in adult compared to neonatal blood after LPS stimulation. Stimulation with LPS resulted in significantly decreased activation of p38 MAPK in neonatal blood, whereas NF-κB showed no difference. Following inhibition of p38 MAPK with the specific inhibitor SB-202190, levels of TNF-α and IL-6 significantly decreased in neonatal and adult blood, whereas pharmacological inhibition of NF-κB with SC-514 showed no significant effect on cytokine expression.
We conclude that p38 MAPK phosphorylation is crucially involved in LPS activation and could explain the differences in early cytokine response between neonatal and adult blood.
败血症仍然是新生儿发病率和死亡率的主要原因。
核因子-κB（NF-κB）和 p38 丝裂原活化蛋白激酶（MAPK）似乎都是炎症反应的关键介质，我们研究了脂多糖（LPS）对新生儿和成人全血中 NF-κB 和 p38 MAPK 表达和功能的影响。
通过流式细胞术分析测定 Th1/Th2 细胞因子浓度以及 NF-κB 和 p38 MAPK 的磷酸化。
LPS 刺激 4 小时后，新生儿和成人血液上清液中 TNF-α、IL-6 和 IL-10 浓度显著升高。IFN-γ、IL-4 和 IL-2 无明显变化。此外，LPS 刺激后成人血液中 TNF-α浓度明显高于新生儿血液。LPS 刺激导致新生儿血液中 p38 MAPK 的激活显著降低，而 NF-κB 则无差异。用特异性抑制剂 SB-202190 抑制 p38 MAPK 后，新生儿和成人血液中的 TNF-α 和 IL-6 水平显著降低，而用 SC-514 抑制 NF-κB 对细胞因子表达无显著影响。
我们得出结论，p38 MAPK 磷酸化在 LPS 激活中起关键作用，可以解释新生儿和成人血液中早期细胞因子反应的差异。
