Elevated interleukin 8 and T-helper 1 and T-helper 17 cytokine levels prior to antiretroviral therapy in participants who developed immune reconstitution inflammatory syndrome during ACTG A5164.

TitleElevated interleukin 8 and T-helper 1 and T-helper 17 cytokine levels prior to antiretroviral therapy in participants who developed immune reconstitution inflammatory syndrome during ACTG A5164.
Publication TypeJournal Article
Year of Publication2012
AuthorsGrant PM, Komarow L, Lederman MM, Pahwa S, Zolopa AR, Andersen J, Asmuth DM, Devaraj S, Pollard RB, Richterman A, Kanthikeel S, Sereti I
JournalJ Infect Dis
Volume206
Issue11
Pagination1715-23
Date Published2012 Dec 1
ISSN1537-6613
KeywordsAdult, Anti-HIV Agents, Biomarkers, Case-Control Studies, Cytokines, Gene Expression Regulation, HIV Infections, Humans, Immune Reconstitution Inflammatory Syndrome, Interleukin-8, Logistic Models, Middle Aged, Risk Factors
Abstract

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear.

METHODS: We performed a nested case-control study using specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19 IRIS and 39 control participants at study entry, ART initiation, and IRIS and used conditional logistic regression to develop IRIS predictive models. We evaluated the effect of corticosteroids on biomarker levels.

RESULTS: Eleven and 8 participants developed paradoxical and unmasking IRIS, respectively, none while still receiving corticosteroids. Compared to controls, cases displayed elevations at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]-γ, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN-γ and TNF were strong predictors of IRIS. Participants who received corticosteroids and later developed IRIS had marked increases in IL-6, IL-8, and IFN-γ at the time of IRIS. T-cell activation markers did not differ in cases and controls prior to ART but were increased in cases at the time of IRIS.

CONCLUSIONS: Increased IL-8, Th1, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.

DOI10.1093/infdis/jis604
Alternate JournalJ. Infect. Dis.
PubMed ID23002445
PubMed Central IDPMC3488199
Grant ListAI38858 / AI / NIAID NIH HHS / United States
AI6863 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI073961 / AI / NIAID NIH HHS / United States
R01 AI077501 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States