Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV prevention trials network-056)
Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV prevention trials network-056)
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DOI：
10.1097/qai.0b013e318156ef16
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Anton, Peter A.
中科院分区：
文献类型：
--
作者：
McGowan, Ian;Elliott, Julie;Anton, Peter A.
目的：本研究的目的是评估粘膜参数的生物学稳定性，这些参数可能用作I期直肠安全性研究的终点。方法：16名男性受试者按HIV感染状况、病毒载量和性行为分为4组。每位参与者每隔2周接受3次乙状结肠镜检查，收集血液、肠活检和直肠分泌物。评估肠道组织学、粘膜单核细胞表型特征、细胞因子信使RNA （mRNA）谱（RANTES、干扰素γ [IFN γ]和白细胞介素-10）和免疫球蛋白分泌。计算类内相关性（ICC）来评估终点稳定性。结果：定性组织学显示95%的活组织检查中>有轻微的炎症，并且在整个研究期间保持稳定。组织细胞因子mRNA测量和几种t细胞表型标记物的CC为>0.7，表明随着时间的推移稳定。粘膜CD4淋巴细胞减少在hiv阳性参与者中可见，在病毒载量较高的参与者中更为明显。细胞因子表达（ifn - γ）和t细胞表型（CD3、CD4、CD8、CD19、CD4/CCR5和CD4/CD38）在10和30 cm处收集的组织样本之间存在适度差异。结论：这些数据有助于为未来一期直肠安全性研究的终点选择提供理论依据。
Objectives: The purpose of this study was to evaluate the biologic stability of mucosal parameters that might be used as endpoints in phase I rectal safety studies.Methods: Sixteen male participants were enrolled into 4 groups defined by HIV status, viral load, and sexual activity. Each participant underwent 3 flexible sigmoidoscopics at 2-week intervals with collection of blood, intestinal biopsies, and rectal secretions. Intestinal histology, phenotypic characterization of mucosal mononuclear cells, cytokine messenger RNA (mRNA) profiles (RANTES, interferon-gamma [IFN gamma], and interleukin-10), and immunoglobulin secretion were assessed. Intraclass correlation (ICC) was calculated to assess endpoint stability.Results: Qualitative histology demonstrated minimal inflammation in >95% of biopsies and remained stable throughout the study period.]CC for the tissue cytokine mRNA measurements and several T-cell phenotypic markers was >0.7, indicating stability over time. Mucosal CD4 lymphopenia was seen in the HIV-positive participants and was more pronounced in those with higher viral loads. Modest differences were observed for cytokine expression (IFN-gamma) and T-cell phenotype (CD3, CD4, CD8, CD19, CD4/CCR5, and CD4/CD38) between the tissue samples collected at 10 and 30 cm.Conclusions: These data help to provide a rationale for the selection of endpoints for future phase I rectal safety studies.