Time-dependent mediators of HPA axis activation following live Escherichia coli.
Time-dependent mediators of HPA axis activation following live Escherichia coli.
复制标题
活大肠杆菌后 HPA 轴激活的时间依赖性介质。
DOI：
10.1152/ajpregu.00301.2011
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Johnson,JD
中科院分区：
文献类型：
--
作者：
Zimomra,ZR;Porterfield,VM;Camp,RM;Johnson,JD
下丘脑-垂体-肾上腺（HPA）轴在免疫挑战期间被激活，释放能量并通过反馈和调节机制调节免疫反应。炎症细胞因子和前列腺素是已知的HPA激活的贡献者；然而，大多数先前的研究只关注LPS给药后的特定时间点。由于整个细菌与LPS相比具有不同的免疫刺激特性，因此本研究的目的是确定在活的大肠杆菌攻击后，不同的免疫产物是否有助于在不同时间激活HPA。给Sprague-Dawley大鼠腹腔注射大肠杆菌（2.5 × 107CFU），观察其循环皮质酮、ACTH、炎症因子和pge2的时间变化。血浆皮质酮在大肠杆菌感染后0.5小时达到峰值，并在4小时后稳定恢复到基线水平。血浆pge2与血浆皮质酮的早期升高相关，而炎症因子直到2小时才被检测到。用吲哚美辛（一种非选择性环加氧酶抑制剂）预处理，完全阻断了血浆皮质酮的早期升高，但在2小时后没有。而IL-6抗体预处理对皮质酮的早期升高没有影响，但在2小时后会减弱皮质酮。有趣的是，吲哚美辛预处理并不能完全阻断高浓度大肠杆菌（2.5 × 108CFU）后皮质酮的早期升高。进一步的研究发现，只有在大肠杆菌之前接受吲哚美辛治疗的动物在早期时间点（0.5和1 h）显示血浆和肝脏细胞因子升高，这表明前列腺素抑制早期炎症细胞因子的产生。总的来说，这些数据表明前列腺素在很大程度上介导了血浆皮质酮的早期升高，而炎症细胞因子有助于在较晚的时间点维持皮质酮水平。
The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 107CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 108CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.