Caso G, Garlick P J, Gelato M C, McNurlan M A
Department of Surgery, State University of New York at Stony Brook, Stony Brook, NY 11794-8191, USA.
Clin Sci (Lond). 2001 Dec;101(6):583-9.
HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease.
已证明HIV感染会影响淋巴细胞功能，并降低体外淋巴细胞对有丝分裂原刺激的反应性，但对于体内淋巴细胞代谢以及疾病过程中其如何受到影响却知之甚少。本研究通过HIV相关疾病的进展来调查体内淋巴细胞的代谢活性。在健康志愿者（n = 7）、HIV阳性但无症状的患者（n = 7）以及艾滋病患者（n = 8）中，用L-[(2)H(5)]苯丙氨酸（45 mg/kg体重）测量淋巴细胞蛋白质合成。与健康对照相比，HIV阳性患者的淋巴细胞蛋白质合成速率[以淋巴细胞蛋白质的百分比表示，即分数合成率（FSR）]未发生改变（分别为7.9±1.28%和9.1±0.53%/天），但艾滋病患者显著升高（14.0±1.16%/天；P<0.05）。细胞因子肿瘤坏死因子-α（TNF-α）的血清浓度随疾病进展而增加，艾滋病患者的TNF-α水平（6.81±0.88 ng/l）显著高于健康对照（3.09±0.27 ng/l；P<0.05）。淋巴细胞蛋白质FSR与血清TNF-α浓度呈正相关（r = 0.55，P = 0.009），与CD4(+)淋巴细胞计数呈负相关（r = -0.70，P = 0.004）。艾滋病患者淋巴细胞蛋白质合成的升高表明淋巴细胞的周转率更高。这可能与免疫系统的全身性激活有关，这在HIV相关疾病晚期血清TNF-α浓度升高中也有所体现。
