Tumor Necrosis Factor<i>α</i>, Interleukin 2, and Soluble Interleukin 2 Receptor Levels in Human Immunodeficiency Virus Type 1-Infected Individuals Receiving Intermittent Cycles of Interleukin 2

Fortis, Claudio; Soldini, Laura; Ghezzi, Silvia; Colombo, Stefania; Tambussi, Giuseppe; Vicenzi, Elisa; Gianotti, Nicola; Nozza, Silvia; Veglia, Fabrizio; Murone, M; Lazzarin, Adriano; Poli, Guido

doi:10.1089/088922202317406637

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…Unadjusted median IL-2 and GM-CSF concentra-tions (Table 3) and adjusted mean concentrations (accounting for lab and lot differences) were lower in HIV ϩ subjects, which is consistent with published reports suggesting defects in production of these two cytokines as a result of HIV infection (6,10,25). In other reports, serum concentrations of IL-2 or GM-CSF were consistently below the level of detection or showed lower median concentrations in HIV ϩ subjects (7,11,14). It is likely, therefore, that the differences detected by the high-sensitivity Linco kit reflect the significantly lower frequency of detectable results in HIV ϩ than HIV Ϫ subjects (for IL-2, 55% versus 78% [P ϭ 0.02]; for GM-CSF, 35% versus 68% [P ϭ 0.007]).…”

Section: Vol 18 2011 Multisite Comparison Of Multiplex Cytokine Asssupporting

confidence: 89%

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Breen

Reynolds

Cox

et al. 2011

Clin Vaccine Immunol

150

130

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The concentrations of cytokines in human serum and plasma can provide valuable information about in vivo immune status, but low concentrations often require high-sensitivity assays to permit detection. The recent development of multiplex assays, which can measure multiple cytokines in one small sample, holds great promise, especially for studies in which limited volumes of stored serum or plasma are available. Four high-sensitivity cytokine multiplex assays on a Luminex (Bio-Rad, BioSource, Linco) or electrochemiluminescence (Meso Scale Discovery) platform were evaluated for their ability to detect circulating concentrations of 13 cytokines, as well as for laboratory and lot variability. Assays were performed in six different laboratories utilizing archived serum from HIV-uninfected and -infected subjects from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) and commercial plasma samples spanning initial HIV viremia. In a majority of serum samples, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha were detectable with at least three kits, while IL-1␤ was clearly detected with only one kit. No single multiplex panel detected all cytokines, and there were highly significant differences (P < 0.001) between laboratories and/or lots with all kits. Nevertheless, the kits generally detected similar patterns of cytokine perturbation during primary HIV viremia. This multisite comparison suggests that current multiplex assays vary in their ability to measure serum and/or plasma concentrations of cytokines and may not be sufficiently reproducible for repeated determinations over a long-term study or in multiple laboratories but may be useful for longitudinal studies in which relative, rather than absolute, changes in cytokines are important.

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Section: Vol 18 2011 Multisite Comparison Of Multiplex Cytokine Asssupporting

confidence: 89%

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Breen

Reynolds

Cox

et al. 2011

Clin Vaccine Immunol

150

130

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“…In addition, this study showed that IL‐2 therapy induced the expansion of CD4 + CD25 + T cells, although CD25 expression was not evaluated in CD8 + T cells. Another study reported that IL‐2 therapy of HIV + individuals increased the release of sCD25, an indicator of disease progression 120 …”

Section: Receptor Expression and γC Cytokine Therapeuticsmentioning

confidence: 99%

“…Another study reported that IL-2 therapy of HIV + individuals increased the release of sCD25, an indicator of disease progression. 120 Given that immune deficiency persists despite increased concentrations of plasma IL-7 in HIV infection, higher IL-7 concentrations may be required to restore T-cell homeostasis and overcome such impaired T-cell function. Therefore, clinical trials are underway to assess the use of IL-7 as a therapeutic agent in HIV infection.…”

Section: Receptor Expression and C C Cytokine Therapeuticsmentioning

confidence: 99%

Expression of γ‐chain cytokine receptors on CD8⁺ T cells in HIV infection with a focus on IL‐7Rα (CD127)

Crawley

Angel

2011

Immunol Cell Biol

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When interleukin‐2 (IL‐2) receptor γ‐chain (γC)‐sharing cytokine receptors on T cells bind their specific ligands (IL‐2, ‐4, ‐7, ‐9, ‐15 or ‐21), they initiate a variety of cell signals that promote survival, differentiation or antiviral or antitumor cytolytic functions. Although expression of the γC is constitutive across T‐cell subsets, the varying expression of other receptor complex components can regulate cytokine signalling and function. Impaired γC cytokine activity in HIV infection, and the role of γC cytokines in CD8+ T‐cell function and homeostasis, implicates these molecules among potential contributors to the observed decline of cytolytic activity (CTL) in HIV disease. In particular, this review will be highlighting information about the IL‐7 receptor (IL‐7R) complex, which is composed of the γC and the IL‐7Rα (CD127) chains. There has been an abundance of HIV‐related CD127 research and its important role in CD8+ T‐cell survival and function. The expression of CD127 undergoes dramatic changes throughout the course of T‐cell responses in HIV infection. The expression of CD127 is significantly decreased in progressive HIV disease, whereas effective antiretroviral therapy results in its recovery. Observations of impaired IL‐7 activity in HIV+ individuals have suggested that CD127 has an important role in HIV immunopathogenesis. In addition, a soluble form of CD127 (sCD127) is upregulated in the plasma of HIV+ individuals. Hence, CD127 is being increasingly considered as a marker of disease prognosis, and related information may provide insight into understanding the expression and role of other γC receptors in HIV disease and contribute to the development of novel cytokine‐based therapeutics.

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“…Interleukin 2 (IL-2) is a critical cytokine required for T cell activation, proliferation, and function [reviewed in (20, 21)]. However, IL-2 also induces secretion of proinflammatory cytokines like IL-6, IL-1β and tumor necrosis factor alpha (TNF-α) (22–24), and is associated with increased levels of inflammatory markers like C-reactive protein (CRP) and D-dimer in the plasma of HIV-infected subjects, independent of HIV viral load (25). In addition, in vitro activation of peripheral blood mononuclear cells (PBMCs) with IL-2 increases HIV production (26, 27).…”

Section: Introductionmentioning

confidence: 99%

GB Virus C Envelope Protein E2 Inhibits TCR-Induced IL-2 Production and Alters IL-2–Signaling Pathways

Bhattarai

McLinden

Xiang

et al. 2012

The Journal of Immunology

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GB virus type C (GBV-C) viremia is associated with reduced CD4+ T cell expansion following Interleukin 2 (IL-2) therapy and with a reduction in T cell activation in HIV-infected individuals. Mechanism(s) by which GBV-C might alter T-cell activation or IL-2 signaling have not been studied. Here, we assess IL-2 release, IL-2 receptor (IL-2R) expression, IL-2 signaling, and cell proliferation in Tet-off Jurkat cells expressing the GBV-C envelope glycoprotein (E2) following activation through the T cell receptor (TCR). TCR activation was induced by incubation in anti-CD3/CD28 antibodies. IL-2 release was measured by ELISA, STAT5 phosphorylation was assessed by immunoblot, and IL-2Rα (CD25) expression and cell proliferation were determined by flow cytometry. IL-2 and IL-2Rα steady-state mRNA levels were measured by real-time PCR. GBV-C E2 expression significantly inhibited IL-2 release, CD25 expression, STAT5 phosphorylation and cellular proliferation in Jurkat cells following activation through the TCR compared to control cell lines. Reducing E2 expression by doxycycline reversed the inhibitory effects observed in the E2-expressing cells. The N-terminal 219 a.a of E2 was sufficient to inhibit IL-2 signaling. Addition of purified recombinant GBV-C E2 protein to primary human CD4+ and CD8+ T cells inhibited TCR activation-induced IL-2 release and upregulation of IL-2Rα expression. These data provide evidence that the GBV-C E2 protein may contribute to the block in CD4+ T cell expansion following IL-2 therapy in HIV-infected individuals. Furthermore, the effects of GBV-C on IL-2 and IL-2 signaling pathways may contribute to the reduction in chronic immune activation observed in GBV-C/HIV co-infected individuals.

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Tumor Necrosis Factorα, Interleukin 2, and Soluble Interleukin 2 Receptor Levels in Human Immunodeficiency Virus Type 1-Infected Individuals Receiving Intermittent Cycles of Interleukin 2

Cited by 9 publications

References 36 publications

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Expression of γ‐chain cytokine receptors on CD8⁺ T cells in HIV infection with a focus on IL‐7Rα (CD127)

GB Virus C Envelope Protein E2 Inhibits TCR-Induced IL-2 Production and Alters IL-2–Signaling Pathways

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Tumor Necrosis Factorα, Interleukin 2, and Soluble Interleukin 2 Receptor Levels in Human Immunodeficiency Virus Type 1-Infected Individuals Receiving Intermittent Cycles of Interleukin 2

Cited by 9 publications

References 36 publications

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Multisite Comparison of High-Sensitivity Multiplex Cytokine Assays

Expression of γ‐chain cytokine receptors on CD8+ T cells in HIV infection with a focus on IL‐7Rα (CD127)

GB Virus C Envelope Protein E2 Inhibits TCR-Induced IL-2 Production and Alters IL-2–Signaling Pathways

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Product

Resources

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Expression of γ‐chain cytokine receptors on CD8⁺ T cells in HIV infection with a focus on IL‐7Rα (CD127)