Norbiato G, Bevilacqua M, Vago T, Clerici M
Department of Endocrinology, University Hospital Luigi Sacco, Milan, Italy.
Ann N Y Acad Sci. 1998 May 1;840:835-47. doi: 10.1111/j.1749-6632.1998.tb09621.x.
Glucocorticoids, the final product of HPA axis, and their receptors (GRs) on mononuclear cells are crucial mediators in the endocrine-immune interaction. An alteration in GRs involving a lower receptor affinity (Kd) for glucocorticoids has been found in a group of advanced AIDS patients, who developed Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis) in spite of hypercortisolism and normal or slightly elevated values of ACTH (AIDS-GR). In these patients, data for the suppression test showed decreased cortisol and ACTH suppression in response to exogenous dexamethasone. The inhibitory effect of dexamethasone on radiolabeled-thymidine incorporation in mononuclear cells from these patients was also reduced. Monocytes of AIDS-GR patients had a receptor Kd of 10.5 +/- 4.2 nmol/l that was higher than that of other AIDS patients (AIDS-C) (2.9 +/- 0.8 nmol/l) and normal subjects (2.0 +/- 0.8 nmol/l: p < 0.01). Correlations were found between plasmatic IFN-alpha and receptor Kd on monocytes of AIDS-GR (r = 0.77). Poly (i)-poly (c)-induced IFN-alpha production by monocytes was inhibited by glucocorticoids in the AIDS-C group and controls (approx. 80% in both groups): The effect was reversed by the receptor antagonist RU-486. By contrast, glucocorticoid did not inhibit IFN-alpha production in AIDS-GR group. In conclusion, levels of plasmatic IFN-alpha, a cytokine with antiviral properties, may be increased several times, and dexamethasone fails to inhibit monocytes' IFN-alpha production only in AIDS with cortisol resistance, a disturbance that confirms an important immunoregulatory role of glucocorticoids in HIV disease.
糖皮质激素作为下丘脑-垂体-肾上腺（HPA）轴的最终产物，及其在单核细胞上的受体（GRs）是内分泌-免疫相互作用的关键介质。在一组晚期艾滋病患者中发现了GRs的改变，即对糖皮质激素的受体亲和力（Kd）较低，尽管这些患者存在高皮质醇血症且促肾上腺皮质激素（ACTH）值正常或略有升高，但仍出现了艾迪生病症状（虚弱、体重减轻、低血压、低钠血症和严重的黏膜皮肤黑色素沉着）（艾滋病-GR）。在这些患者中，抑制试验数据显示，对外源性地塞米松的反应中，皮质醇和ACTH的抑制作用减弱。地塞米松对这些患者单核细胞中放射性标记胸腺嘧啶核苷掺入的抑制作用也降低。艾滋病-GR患者的单核细胞受体Kd为10.5±4.2 nmol/l，高于其他艾滋病患者（艾滋病-C）（2.9±0.8 nmol/l）和正常受试者（2.0±0.8 nmol/l：p<0.01）。在艾滋病-GR患者的单核细胞中，血浆干扰素-α（IFN-α）与受体Kd之间存在相关性（r = 0.77）。在艾滋病-C组和对照组中，糖皮质激素抑制了多聚肌苷酸-多聚胞苷酸（Poly (i)-Poly (c)）诱导的单核细胞产生IFN-α（两组均约为80%）：该作用可被受体拮抗剂RU-486逆转。相比之下，糖皮质激素在艾滋病-GR组中并未抑制IFN-α的产生。总之，具有抗病毒特性的细胞因子血浆IFN-α水平可能会升高数倍，且仅在伴有皮质醇抵抗的艾滋病患者中，地塞米松无法抑制单核细胞产生IFN-α，这种紊乱证实了糖皮质激素在HIV疾病中具有重要的免疫调节作用。
