Januszkiewicz A, Essén P, McNurlan M A, Ringdén O, Garlick P J, Wernerman J
Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
Metabolism. 2001 Nov;50(11):1308-14. doi: 10.1053/meta.2001.27204.
In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.
作为人类创伤模型,给健康志愿者输注复合应激激素后,其体内单核细胞的蛋白质合成减少。在此,目的是进一步研究这一发现,并测量分离的T淋巴细胞的体内蛋白质合成。此外,还阐明了应激激素对淋巴细胞亚群和单核细胞的影响,通过流式细胞术以及体外植物血凝素(PHA)诱导和未刺激的增殖反应来表征。将16名健康志愿者随机分为两组,分别接受应激激素或生理盐水输注6小时。通过测量稳定同位素标记的苯丙氨酸掺入淋巴细胞和单核细胞蛋白质中的情况,研究治疗前后的体内蛋白质合成。应激激素输注后,两个细胞群体的蛋白质合成均下降:T淋巴细胞从13.0%±0.7%/天(平均值±标准差)降至8.6%±2.1%/天(P<.01),单核细胞从13.3%±1.2%/天降至6.3±2.0%/天(P<.001)。体外增殖反应未观察到变化。应激激素输注使辅助性T细胞CD3/CD4的百分比从41%降至18%(P<.001),细胞毒性T细胞CD3/CD8从27%降至15%(P<.001),以及总T细胞CD3从69%降至35%(P<.001)。自然杀伤(NK)细胞CD16/CD56的百分比从17%增至55%(P<.001)。对活化T淋巴细胞上表达的表型进行测定表明,应激激素组中CD3/HLA-DR未变,而CD3/CD25从14%降至7%(P<.01)。研究表明,在6小时应激激素输注后立即测定时,T淋巴细胞体内蛋白质合成减少34%,而单核细胞减少53%。这种变化与除NK细胞外所有淋巴细胞亚群的显著减少有关,NK细胞则大幅增加。