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Discordance between peripheral and colonic markers of inflammation during suppressive ART
Richard M Dunham1, Ivan Vujkovic-Cvijin, Steven A Yukl
1*HIV Discovery Performance Unit, GlaxoSmithKline, Research Triangle Park, NC; †Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA (P'ng Loke is now with the Department of Microbiology, Division of Parasitology, New York University Medical Center, New York, NY); ‡Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA; §Division of Infectious Diseases, Department of Medicine, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, CA; ‖Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH; ¶Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA; and #Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
Objective:
Persistent systemic inflammation is associated with the inability of some HIV-infected patients to normalize circulating CD4 T-cell levels after years of suppressive antiretroviral therapy. In this study, we sought to understand whether such systemic inflammation is also associated with detectable signs of inflammation in biopsies from the rectosigmoid colon.
Design:
Immunologic and virological parameters were studied in the peripheral blood and in rectosigmoid colon biopsies from individuals with viral suppression for at least 2 years and with peripheral CD4 T-cell levels of <350 cells per cubic millimeter (immunologic nonresponders, n = 18) or >500 cells per cubic millimeter (immunologic responders, n = 16).
Methods:
Peripheral blood and rectosigmoid colon biopsies were analyzed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction.
Results:
Nonresponders had elevated T-cell activation and inflammatory cytokines in the circulation, but inflammatory gene expression in colon biopsies was not different as compared with responders, and there was little relationship between blood and colon markers of inflammation. Blood inflammatory markers were positively associated with soluble CD14 levels indicative of monocyte activation.
Conclusions:
These findings demonstrate that, in the context of treated HIV disease, it is easier to detect parameters of inflammation (including blood monocyte activation) in the peripheral blood than in isolated rectosigmoid colon biopsies. Accordingly, interventions to block such inflammation in this population might be most conveniently and accurately assessed in blood.
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