Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV Prevention Trials Network-056).
作者： Ian McGowan , Julie Elliott , Galen Cortina , Karen Tanner , Chomchay Siboliban
DOI: 10.1097/QAI.0B013E318156EF16
关键词: Rectal microbicide 、 Viral load 、 Cytokine 、 Immunoglobulin secretion 、 Lentivirus 、 Peripheral blood mononuclear cell 、 Immunology 、 Biology 、 Histology 、 CD8
摘要: OBJECTIVES The purpose of this study was to evaluate the biologic stability mucosal parameters that might be used as endpoints in phase 1 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 sigmoidoscopies at 2-week intervals with collection blood, intestinal biopsies, secretions. Intestinal histology, phenotypic characterization mononuclear cells, cytokine messenger RNA (mRNA) profiles (RANTES, interferon-gamma [IFNgamma], interleukin-10), immunoglobulin secretion assessed. Intraclass correlation (ICC) calculated assess endpoint stability. RESULTS Qualitative histology demonstrated minimal inflammation >95% biopsies remained stable throughout period. ICC for tissue mRNA measurements several T-cell markers >0.7, indicating over time. Mucosal CD4 lymphopenia seen HIV-positive more pronounced those higher loads. Modest differences observed expression (IFNgamma) phenotype (CD3, CD4, CD8, CD19, CD4/CCR5, CD4/CD38) between samples collected 10 30 cm. CONCLUSIONS These data help provide a rationale selection future
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