Christeff N, Gherbi N, Mammes O, Dalle M T, Gharakhanian S, Lortholary O, Melchior J C, Nunez E A
Laboratoire de Biochimie Endocrinienne/Biochimie B, Faculté de Médecine/Hôpital X. Bichat, Paris, France.
Psychoneuroendocrinology. 1997;22 Suppl 1:S11-8. doi: 10.1016/s0306-4530(97)00015-2.
The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.
HIV感染的进展伴随着严重的免疫抑制和恶病质，尤其是在晚期。免疫抑制主要是由于CD4细胞数量急剧下降。体重减轻主要是由于去脂体重减少，而脂肪组织无变化。我们测定了HIV阳性男性血清皮质醇和脱氢表雄酮（DHEA）的浓度及其与绝对CD4细胞计数和体重变化的相关性。五项回顾性和前瞻性研究的结果表明，HIV感染患者血清皮质醇和DHEA的浓度与HIV阴性对照者不同。在感染的各个阶段，血清皮质醇均升高（+20%至+50%，p<.05至p<.001），尤其是在艾滋病患者（IV C期）。相比之下，血清DHEA浓度与HIV感染阶段密切相关，早期（II期和III期或CD4>500）高于晚期（IV C期或CD4<500），晚期低于HIV阴性男性或对照组（+40%至100%，p<.01至p<.001）。CD4细胞计数与皮质醇呈负线性相关（r=-0.4，p<.02），与DHEA呈正线性相关（r=+0.36，p<.01）。体重变化与血清皮质醇之间无显著相关性。相比之下，血清DHEA与体重变化百分比呈负相关（r=-0.69，p<.0001），与皮质醇/DHEA比值呈正相关（r=+0.61，p<.0001）。因此，肾上腺类固醇的循环浓度与HIV感染期间免疫抑制和恶病质的进展之间存在联系。这就提出了一个问题，即临床进展与循环类固醇浓度之间是否存在因果关系。对皮质醇/DHEA比值与免疫反应和恶病质之间关系的进一步研究应能表明这些类固醇对HIV感染病因的作用，并导致新治疗策略的开发。
