Clerici M, Galli M, Bosis S, Gervasoni C, Moroni M, Norbiato G
Cattedra di Immunologia, Università di Milano, DISP LITA Vialba, Milano, Italy.
Ann N Y Acad Sci. 2000;917:956-61. doi: 10.1111/j.1749-6632.2000.tb05462.x.
Alterations in the production of adrenal steroids and a complex pattern of dysregulation in cytokine profiles accompany the progression of HIV infection. Cortisol levels increase in HIV infection, while those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. A shift from type-1 to type-2 cytokine production is also detected in most patients during disease progression. This shift is summarized as a defective production of interferon gamma (IFN gamma), interleukin-2 (IL), and IL-12 accompained by increased production of IL-4, IL-5, IL-6, and IL-10. IFN gamma and IL-2 are suppressed, while the generation of IL-4 is stimulated by cortisol and pharmacological doses of glucocorticoids (GC). GC and IL-4 stimulate the differentiation of B lymphocytes into IgE-producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induces programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes. Because (1) TH1 but not TH2 undergo rapid Fas-mediated PCD upon antigen-stimulation, and (2) TH2 clones preferentially survive in vitro cell cultures, the progressive shift from type-1 to type-2 cytokine production observed in HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. Progression of HIV infection to AIDS can be controlled by highly active antiretroviral therapy (HAART); HAART drastically reduces HIV plasma viremia, but is less effective in immune reconstitution. Additionally HAART is associated in a sizable portion of patients by complex lypodistropyc phenomena that often involve the endocrine system.
随着HIV感染的进展，肾上腺类固醇生成的改变以及细胞因子谱的复杂失调模式随之出现。HIV感染时皮质醇水平升高，而皮质醇免疫调节活性的生理拮抗剂脱氢表雄酮（DHEA）水平降低。在疾病进展过程中，大多数患者还检测到从1型细胞因子产生向2型细胞因子产生的转变。这种转变表现为干扰素γ（IFNγ）、白细胞介素-2（IL-2）和IL-12产生缺陷，同时IL-4、IL-5、IL-6和IL-10产生增加。IFNγ和IL-2受到抑制，而皮质醇和药理剂量的糖皮质激素（GC）刺激IL-4的产生。GC和IL-4刺激B淋巴细胞分化为产生IgE的浆细胞，其浓度在HIV感染时升高。最后，GC在包括成熟T淋巴细胞在内的多种不同细胞中诱导程序性细胞死亡（PCD）。由于（1）TH1而非TH2在抗原刺激后会迅速经历Fas介导的PCD，且（2）TH2克隆在体外细胞培养中优先存活，因此在HIV感染中观察到的从1型细胞因子产生向2型细胞因子产生的逐渐转变可能至少部分是由皮质醇产生增加和DHEA减少所引发的。HIV感染进展至艾滋病可通过高效抗逆转录病毒疗法（HAART）得到控制；HAART可大幅降低HIV血浆病毒血症，但在免疫重建方面效果较差。此外，相当一部分患者会出现与HAART相关的复杂脂肪代谢障碍现象，这些现象常涉及内分泌系统。
