Almeida Maria, Cordero Miguel, Almeida Julia, Orfao Alberto
Department of Medicine, University of Salamanca, University of Salamanca, Spain.
Curr HIV Res. 2007 May;5(3):325-36. doi: 10.2174/157016207780636524.
HIV-1 infection is associated with dysregulation of cytokine production by peripheral blood (PB) monocytes and dendritic cells (DC), but controversial results have been reported. We aimed to analyze the effect of antiretroviral therapy (ART) on the in vitro production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin -CD33(high+ ) myeloid DC (mDC) and CD33(+)/CD14(-/dim+)/CD16(high+) DC- from HIV-1+ patients and its relationship with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro cytokine production was analyzed at the single cell level in 32 HIV-1+ patients, grouped according to the number of CD4+ T-cells/microl in PB (<200 CD4 versus >200 CD4). Patients were tested prior to therapy and at weeks +2, +4, +8, +12 and +52 after ART. Prior to ART, production of IL-6, TNF-alpha and IL-12 by mDC and of IL-8 and IL-12 by CD16+ DC was significantly increased among >200 CD4 patients. After one year of ART, increased production of IL-8 by monocytes, of TNF-alpha by mDC and of IL-1beta, IL-6 and TNF-alpha by CD16+ DC was specifically observed among <200 CD4 HIV-1+ individuals showing a high recovery of PB CD4+ T-cell counts. In turn, we found that the significantly reduced percentage of IL-1beta, IL-6, IL-8 and TNF-alpha-producing monocytes and of IL-6 and IL-8-producing mDC and CD16+ DC, as well as the significantly diminished mean amount of IL-6 produced per monocyte, mDC and CD16+ DC and of IL-12 produced per CD16+ DC observed at week +52 for the >200 CD4 patients, were related to the presence of co-infection with HCV. In summary, HIV-1+ individuals show abnormal production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin even after one year of ART, such abnormalities being associated with the degree of recovery of PB CD4+ T-cell counts in more immunocompromised patients and HCV co-infection in more immunocompetent HIV-1+ individuals.
HIV-1感染与外周血（PB）单核细胞和树突状细胞（DC）的细胞因子产生失调有关，但已有相互矛盾的结果报道。我们旨在分析抗逆转录病毒疗法（ART）对HIV-1阳性患者经PB刺激的单核细胞以及髓系来源的DC（CD33高表达的髓系DC（mDC）和CD33阳性/CD14阴性/弱阳性/CD16高表达DC）体外产生炎性细胞因子的影响，及其与CD4+T细胞恢复和丙型肝炎病毒（HCV）合并感染的关系。在32例HIV-1阳性患者中，根据PB中每微升CD4+T细胞的数量（<200个CD4对>200个CD4）进行分组，在单细胞水平分析体外细胞因子的产生情况。在接受ART治疗前以及治疗后第2、4、8、12和52周对患者进行检测。在ART治疗前，>200个CD4的患者中，mDC产生IL-6、TNF-α和IL-12以及CD16+DC产生IL-8和IL-12的水平显著升高。在接受ART治疗一年后，在PB CD4+T细胞计数恢复良好的<200个CD4的HIV-1阳性个体中，特别观察到单核细胞产生IL-8、mDC产生TNF-α以及CD16+DC产生IL-1β、IL-6和TNF-α的水平增加。反过来，我们发现，对于>200个CD4的患者，在第52周时，产生IL-1β、IL-6、IL-8和TNF-α的单核细胞以及产生IL-6和IL-8的mDC和CD16+DC的百分比显著降低，并且每个单核细胞、mDC和CD16+DC产生的IL-6平均量以及每个CD16+DC产生的IL-12平均量显著减少，这与合并感染HCV有关。总之，即使在接受ART治疗一年后，HIV-1阳性个体经PB刺激的髓系来源单核细胞和DC仍表现出炎性细胞因子产生异常，这种异常与免疫功能较差患者的PB CD4+T细胞计数恢复程度以及免疫功能较强的HIV-1阳性个体合并感染HCV有关。
