JAIDS Journal of Acquired Immune Deficiency Syndromes. 37(2):1228-1236, OCTOBER 1ST, 2004
DOI: 10.1097/01.qai.0000131846.12453.29
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PMID: 15385729
Issn Print: 1525-4135
Publication Date: October 1st, 2004
Increased HIV-1 Mucosal Replication Is Associated With Generalized Mucosal Cytokine Activation
Ian McGowan;Julie Elliott;Marie Fuerst;Philip Taing;John Boscardin;Michael Poles;Peter Anton;
+ Author Information
From the *Center for HIV and Digestive Diseases, Division of Digestive Diseases, University of California at Los Angeles (UCLA) AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA; and †Department of Medicine, New York University School of Medicine, New York, NY.
Abstract
The purpose of this study was to characterize intestinal mucosal cytokine profiles in subjects with HIV-1 infection and their relation to mucosal viral load (MVL). Intestinal mucosal cytokine mRNA (interleukin [IL]-2, interferon [IFN]-γ, IL-12, IL-10, IL-1β, tumor necrosis factor [TNF]-α, IL-6, and regulated upon activation, normal T-cell expressed and secreted [RANTES]) and HIV-1 RNA were quantified using real-time polymerase chain reaction (PCR). On the basis of MVL quantification, the HIV-1–infected subjects were divided into 3 groups: undetectable MVL (<50 copies/μg of tissue total RNA), low MVL (>50 but <5000 copies/μg of tissue total RNA), and high MVL (>5000 copies/μg of tissue total RNA). Compared with the control group, significant reductions in RANTES, IL-2, and IFNγ expression were seen in the undetectable MVL group (P < 0.005). IL-6 was significantly increased in all the HIV groups (P < 0.005), and RANTES, IL-10, and IFNγ were increased in the high MVL group (P < 0.005). Subjects with high MVL have generalized immune activation with increases in T helper (Th)1, Th2, and proinflammatory cytokines, whereas subjects with undetectable MVL have reduced expression of multiple cytokines. The pathologic basis for these observations is unclear but may relate to the success or failure of antiretroviral therapy in controlling mucosal viral replication.
