Source
Center for Prevention Research in the Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of Clifornia, Los Angeles, Los Angeles, CA, USA. mcgowanim@mail.magee.edu
Abstract
OBJECTIVES:
The purpose of this study was to evaluate the biologic stability of 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 of blood, intestinal biopsies, and rectal secretions. Intestinal histology, phenotypic characterization of mucosal mononuclear cells, cytokine messenger RNA (mRNA) profiles (RANTES, interferon-gamma [IFNgamma], 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. ICC 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 (IFNgamma) 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 1 rectal safety studies.