Raised cortisol:DHEAS ratios in the elderly after injury:: potential impact upon neutrophil function and immunity
Raised cortisol:DHEAS ratios in the elderly after injury:: potential impact upon neutrophil function and immunity
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DOI：
10.1111/j.1474-9726.2005.00178.x
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发表时间：
2005-12-01
期刊：
影响因子：
7.8
通讯作者：
Lord, JM
中科院分区：
文献类型：
--
作者：
Butcher, SK;Killampalli, V;Lord, JM
压力对免疫反应的有害影响随着年龄的增长而增加，尽管其机制尚不完全清楚。对压力的生理反应部分由肾上腺皮质系统调节。肾上腺激素脱氢表雄酮硫酸盐(DHEAS)和皮质醇对先天性免疫系统有相反的作用，DHEAS增强而皮质醇抑制免疫，皮质醇与DHEAS的摩尔比随着年龄的增加而增加。我们发现，老年髋部骨折患者在受伤后产生了强烈的中性粒细胞，但循环中的中性粒细胞显示出受损的抗菌反应。因此，我们认为肾上腺皮质激素介导了老年人受伤后免疫抑制的加剧。我们检测了老年(65岁)髋部骨折患者和年龄匹配的健康对照组的中性粒细胞功能和肾上腺皮质激素水平。在35名老年患者中，有13人在髋部骨折后感染。老年髋部骨折患者的中性粒细胞超氧化物生产低于对照组(P<；0.005)，损伤后感染的患者低于未感染的患者(P<；0.05)。老年髋部骨折患者的血清皮质醇/dheas比值(0.56±0.38)高于年龄匹配的对照组(0.36±0.21；P<；0.05)和青年骨折患者(0.087±0.033；P<；0.0001)。此外，与未死于感染的老年患者相比，死于感染的老年患者皮质醇水平升高(0.803+/-0.42vs 0.467+/-0.28；P<；0.02)。在体外，皮质醇显着减少中性粒细胞超氧化物的产生(P<；0.05)，这可以通过与DHEAS共同孵育来阻止。我们认为，皮质醇：dheas比率的增加可能导致老年人在身体应激后免疫力下降。
The detrimental effect of stress on the immune response increases with age, though the mechanisms responsible are not fully understood. The physiological response to stress is regulated in part by the adrenocortical system. Adrenal hormones dehydroepiandrosterone sulphate (DHEAS) and cortisol have opposing effects on the innate immune system, DHEAS enhances while cortisol suppresses immunity and the molar ratio of cortisol to DHEAS increases with age. We found that elderly hip fracture patients produced a robust neutrophilia after injury, but circulating neutrophils showed an impaired antibacterial response. We therefore proposed that adrenocortical hormones mediate the heightened immunosuppression seen in the elderly after injury. We examined neutrophil function and adrenocortical hormone levels in elderly (> 65 years) hip fracture patients and age-matched healthy controls. Thirteen out of 35 elderly patients acquired infections following hip fracture. Neutrophil superoxide production was lower in elderly hip fracture patients compared with controls (P < 0.005) and lower in patients who acquired infection following injury compared with those who did not (P < 0.05). Serum cortisol:DHEAS ratio was higher in elderly hip fracture patients (0.56 +/- 0.38) compared with either age-matched controls (0.36 +/- 0.21; P < 0.05) or young fracture patients (0.087 +/- 0.033; P < 0.0001). Moreover, cortisol: DHEAS was increased in elderly patients who succumbed to infection compared with those who did not (0.803 +/- 0.42 vs. 0.467 +/- 0.28; P < 0.02). In vitro cortisol significantly decreased neutrophil superoxide generation (P < 0.05) and this was prevented by coincubation with DHEAS. We propose that increased cortisol:DHEAS ratios may contribute to reduced immunity following physical stress in the elderly.