Stylianou E, Aukrust P, Nordøy I, Müller F, Frøland S S
Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department, Rikshopitalet, Oslo, Norway.
APMIS. 2000 Sep;108(9):601-7. doi: 10.1034/j.1600-0463.2000.d01-1410.x.
Based on the potentially important role of IL-10 and IL-12 in the pathogenesis of HIV infection, we have examined the effect of highly active antiretroviral therapy (HAART) on the production of these two cytokines, and whether addition of IL-12 or anti-IL-10 in vitro could improve the proliferative response in peripheral blood mononuclear cells (PBMC) from HIV-infected patients during such therapy. Our findings are: (i) After initiating HAART there were no significant changes in PHA- or MAC-PPD-stimulated IL-10 and IL-12 levels in PBMC supernatants in the patient group as a whole. (ii) However, while a decline in IL-10 synthesis was shown in patients with high baseline MAC-PPD- and PHA-stimulated IL-10 levels, IL-10 increased in patients with lower baseline levels. A similar pattern was seen for MAC-PPD-stimulated IL-12 levels. (iii) Exogenously added IL-12 and anti-IL-10 markedly and additively improved MAC-PPD-stimulated PBMC proliferation in vitro. Thus, a loss of cell-mediated immune response exists in HIV-infected patients also during apparently successful HAART and this can be significantly improved by addition of IL-12 and anti-IL-10, at least in vitro. These results suggest that further exploration of both IL-10 and IL-12 as targets for immunomodulating therapy in HIV-infected patients in addition to HAART might be important.
基于白细胞介素-10（IL-10）和白细胞介素-12（IL-12）在HIV感染发病机制中可能发挥的重要作用，我们研究了高效抗逆转录病毒疗法（HAART）对这两种细胞因子产生的影响，以及在体外添加IL-12或抗IL-10是否能改善接受此类治疗的HIV感染患者外周血单个核细胞（PBMC）的增殖反应。我们的研究结果如下：（i）在开始HAART后，整个患者组PBMC上清液中，经植物血凝素（PHA）或结核菌素纯蛋白衍生物（MAC-PPD）刺激后的IL-10和IL-12水平无显著变化。（ii）然而，基线MAC-PPD和PHA刺激后IL-10水平较高的患者，其IL-10合成下降，而基线水平较低的患者IL-10升高。MAC-PPD刺激后的IL-12水平也呈现类似模式。（iii）外源性添加IL-12和抗IL-10能显著且协同地改善体外MAC-PPD刺激的PBMC增殖。因此，即使在HAART治疗看似成功的情况下，HIV感染患者仍存在细胞介导免疫反应缺失的情况，至少在体外，添加IL-12和抗IL-10可显著改善这一情况。这些结果表明，除HAART外，进一步探索将IL-10和IL-12作为HIV感染患者免疫调节治疗靶点可能具有重要意义。
