A Potential Mechanism for Immune Suppression by Beta-Adrenergic Receptor Stimulation following Traumatic Injury.
A Potential Mechanism for Immune Suppression by Beta-Adrenergic Receptor Stimulation following Traumatic Injury.
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DOI：
10.1159/000486972
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发表时间：
2018
影响因子：
5.3
通讯作者：
O'Keefe GE
中科院分区：
文献类型：
--
作者：
Shubin NJ;Pham TN;Staudenmayer KL;Parent BA;Qiu Q;O'Keefe GE
β-肾上腺素能药物抑制炎症，可能在创伤后感染中发挥重要作用。机制可能包括抑制MAP激酶信号传导。我们试图确定MKP-1是否有助于儿茶酚胺对先天免疫的抑制，也想知道创伤后早期儿茶酚胺治疗是否会增加后来医院感染的风险。我们使用健康人的THP-1细胞和外周血单个核细胞进行实验。我们将细胞暴露于肾上腺素和/或LPS中，并测量炎症基因转录和MAP激酶激活。我们抑制MKP-1活性，以确定其在儿茶酚胺诱导的免疫抑制中的作用。最后，我们研究了受伤的受试者，以确定早期儿茶酚胺治疗是否与医院感染有关。肾上腺素增加MKP-1转录本和蛋白，减少lps诱导的p38和JNK磷酸化以及TNF-α基因。RNAi抑制MKP-1至少部分恢复lps诱导的TNF-α基因表达（p值= 0.024）。在临床队列中，接受β -肾上腺素能药物治疗的受试者发生呼吸机相关性肺炎（aOR = 1.9; 95% CI = 1.3 - 2.6）和菌血症（aOR = 1.5; 95% CI = 1.1 - 2.3）的风险增加。MKP-1可能在儿茶酚胺诱导的先天免疫抑制中起作用，外源性儿茶酚胺可能增加医院感染风险。
β-adrenergic agents suppress inflammation and may play an important role in post-traumatic infections. Mechanisms may include inhibition of MAP kinase signaling. We sought to determine whether MKP-1 contributed to catecholamine suppression of innate immunity and also wanted to know whether early catecholamine treatment after traumatic injury increases the risk for later nosocomial infection. We performed experiments using THP-1 cells and peripheral blood mononuclear cells from healthy individuals. We exposed cells to epinephrine and/or LPS and measured inflammatory gene transcription and MAP kinase activation. We inhibited MKP-1 activity to determine its role in catecholamine-induced immune suppression. Finally, we studied injured subjects to determine whether early catecholamine treatment was associated with nosocomial infection. Epinephrine increases MKP-1 transcripts and protein and a reduction in LPS-induced p38 and JNK phosphorylation and in TNF-α gene. RNAi inhibition of MKP-1 at least partially restores LPS-induced TNF-α gene expression (p-value = 0.024). In the clinical cohort, subjects treated with beta-adrenergic agents had an increased risk of ventilator-associated pneumonia (aOR = 1.9; 95% CI = 1.3 – 2.6) and of bacteremia (aOR = 1.5; 95% CI = 1.1 – 2.3). MKP-1 may have a role in catecholamine-induced suppression of innate immunity and exogenous catecholamines might contribute to nosocomial infection risk.
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脓毒症病理生理学、慢性危重疾病、持续性炎症-免疫抑制和分解代谢综合征。
影响因子：
8.8
作者：
Mira JC;Gentile LF;Mathias BJ;Efron PA;Brakenridge SC;Mohr AM;Moore FA;Moldawer LL
通讯作者：
Moldawer LL
影响因子：
4.8
作者：
Lee, KY;Chang, WT;Rosen, GD
通讯作者：
Rosen, GD
影响因子：
3.7
作者：
Belletti, Alessandro;Musu, Mario;Landoni, Giovanni
通讯作者：
Landoni, Giovanni
影响因子：
3.7
作者：
Lee J;An JN;Hwang JH;Kim YL;Kang SW;Yang CW;Kim NH;Oh YK;Lim CS;Kim YS;Lee JP
通讯作者：
Lee JP
影响因子：
2.6
作者：
Chen, BJ
通讯作者：
Chen, BJ