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

Philip M. Grant, Lauren Komarow, Michael M. Lederman, Savita Pahwa, Andrew R. Zolopa, Janet Andersen, David Asmuth, Sridevi Devaraj, Richard B Pollard, Aaron Richterman, Sudheesh Kanthikeel, Irini Sereti

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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]-, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN- 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- 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.

Original languageEnglish (US)
Pages (from-to)1715-1723
Number of pages9
JournalJournal of Infectious Diseases
Volume206
Issue number11
DOIs
StatePublished - Dec 1 2012

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Immune Reconstitution Inflammatory Syndrome
Interleukin-8
Cytokines
Therapeutics
Interferons
Adrenal Cortex Hormones
Tumor Necrosis Factor-alpha
Biomarkers
Logistic Models
Interleukin-17
T-Lymphocyte Subsets
Interleukin-2

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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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. / Grant, Philip M.; Komarow, Lauren; Lederman, Michael M.; Pahwa, Savita; Zolopa, Andrew R.; Andersen, Janet; Asmuth, David; Devaraj, Sridevi; Pollard, Richard B; Richterman, Aaron; Kanthikeel, Sudheesh; Sereti, Irini.

In: Journal of Infectious Diseases, Vol. 206, No. 11, 01.12.2012, p. 1715-1723.

Research output: Contribution to journalArticle

Grant, Philip M. ; Komarow, Lauren ; Lederman, Michael M. ; Pahwa, Savita ; Zolopa, Andrew R. ; Andersen, Janet ; Asmuth, David ; Devaraj, Sridevi ; Pollard, Richard B ; Richterman, Aaron ; Kanthikeel, Sudheesh ; Sereti, Irini. / 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. In: Journal of Infectious Diseases. 2012 ; Vol. 206, No. 11. pp. 1715-1723.
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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]-, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN- 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- 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.",
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AU - Grant, Philip M.

AU - Komarow, Lauren

AU - Lederman, Michael M.

AU - Pahwa, Savita

AU - Zolopa, Andrew R.

AU - Andersen, Janet

AU - Asmuth, David

AU - Devaraj, Sridevi

AU - Pollard, Richard B

AU - Richterman, Aaron

AU - Kanthikeel, Sudheesh

AU - Sereti, Irini

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N2 - 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]-, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN- 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- 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.

AB - 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]-, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN- 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- 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.

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