Acute stress response in children with meningococcal sepsis: Important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors
Acute stress response in children with meningococcal sepsis: Important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors
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DOI：
10.1210/jc.87.7.3118
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发表时间：
2002-07-01
影响因子：
5.8
通讯作者：
Hokken-Koelega, ACS
中科院分区：
文献类型：
--
作者：
De Groof, F;Joosten, KFM;Hokken-Koelega, ACS
感染性休克是脑膜炎球菌病最严重的临床表现，主要见于 5 岁以下儿童。阐明危重儿童 GH/IGF-I 轴改变的研究非常有限。我们评估了 27 名因脑膜炎球菌败血症导致严重感染性休克的儿童入院后 3 天内的 GHAGF-I 轴以及 IGF 结合蛋白 (IGFBP)、IGFBP-3 蛋白酶、葡萄糖、胰岛素和细胞因子的水平。中位年龄为 22 个月（范围 4-185 个月）。八名患者死亡。在 6 小时 GH 分析中，非幸存者的 GH 水平极高，与幸存者的平均 GH 水平存在显着差异（131 vs. 7 mU/L；P < 0.01）。非幸存者和幸存者之间总IGF-I（2.6 vs. 5.6 nmol/L）、游离IGF-I（0.003 vs. 0.012 nmol/L）、IGFBP-I（44.3 vs. 8.9 nmol/Liter）、IGFBP-3蛋白酶活性（61 vs. 32%）、IL-6（1200）水平存在显着差异。 vs. 50 ng/ml) 和 TNFα (34 vs. 5.3 pg/ml；P < 0.01)。儿科死亡风险评分与 IGFBP-1、IGFBP-3 蛋白酶活性、IL-6 和 TNFa 水平（r +0.45 至 +0.69）以及总 IGF-I 和游离 IGF-I 水平（r 分别 = -0.44 和 -0.55）显着相关。 48小时后的随访显示，与入院时相比，幸存者的GH峰值数量增加，游离IGF-I和IGFBP-3水平增加，IGFBP-1水平降低。非幸存者中 GH 水平和 IGFBP-1 水平极度升高，而总 IGF-I 水平和游离 IGF-I 水平显着降低，并伴有细胞因子 IL-6 和 TNFα 水平升高。这些价值观与幸存者的价值观不同。根据这些发现和文献数据，构建了一个假设模型，总结了我们目前对各种机制的知识和理解。
Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GHAGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/Iiter; P < 0.01). Significant differences were found between non-survivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-I (44.3 vs. 8.9 nmol/Iiter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFa (r +0.45 to +0.69) and with levelsof total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the eytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.