Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

Andreas Ronit, Ronni R Plovsing, Julie C Gaardbo, Ronan M G Berg, Hans J Hartling, Henrik Ullum, Åse B Andersen, Hans O Madsen, Kirsten Møller, Susanne D Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers. Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and after 2, 4, 6, 8, and 24 hours for flow cytometry. CD4(+)CD25(+)CD127lowFoxp3(+) regulatory T cells (Tregs), CD4(+)CD161(+) cells, and activated Human leukocyte antigen, HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T-cell cytokine production.

OriginalsprogEngelsk
TidsskriftJournal of Intensive Care Medicine
Vol/bind32
Udgave nummer1
Sider (fra-til)77-85
ISSN0885-0666
DOI
StatusUdgivet - 2016

Fingeraftryk

Endotoxemia
Lymphopenia
Toll-Like Receptor 4
Interleukin-17
Phytohemagglutinins
Interleukin-10
Interleukin-2
Interleukin-6
Flow Cytometry
Tumor Necrosis Factor-alpha

Citer dette

Ronit, A., Plovsing, R. R., Gaardbo, J. C., Berg, R. M. G., Hartling, H. J., Ullum, H., ... Nielsen, S. D. (2016). Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia. Journal of Intensive Care Medicine, 32(1), 77-85. https://doi.org/10.1177/0885066615606673
Ronit, Andreas ; Plovsing, Ronni R ; Gaardbo, Julie C ; Berg, Ronan M G ; Hartling, Hans J ; Ullum, Henrik ; Andersen, Åse B ; Madsen, Hans O ; Møller, Kirsten ; Nielsen, Susanne D. / Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia. I: Journal of Intensive Care Medicine. 2016 ; Bind 32, Nr. 1. s. 77-85.
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title = "Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia",
abstract = "Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers. Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and after 2, 4, 6, 8, and 24 hours for flow cytometry. CD4(+)CD25(+)CD127lowFoxp3(+) regulatory T cells (Tregs), CD4(+)CD161(+) cells, and activated Human leukocyte antigen, HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T-cell cytokine production.",
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Ronit, A, Plovsing, RR, Gaardbo, JC, Berg, RMG, Hartling, HJ, Ullum, H, Andersen, ÅB, Madsen, HO, Møller, K & Nielsen, SD 2016, 'Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia', Journal of Intensive Care Medicine, bind 32, nr. 1, s. 77-85. https://doi.org/10.1177/0885066615606673

Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia. / Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C; Berg, Ronan M G; Hartling, Hans J; Ullum, Henrik; Andersen, Åse B; Madsen, Hans O; Møller, Kirsten; Nielsen, Susanne D.

I: Journal of Intensive Care Medicine, Bind 32, Nr. 1, 2016, s. 77-85.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

AU - Ronit, Andreas

AU - Plovsing, Ronni R

AU - Gaardbo, Julie C

AU - Berg, Ronan M G

AU - Hartling, Hans J

AU - Ullum, Henrik

AU - Andersen, Åse B

AU - Madsen, Hans O

AU - Møller, Kirsten

AU - Nielsen, Susanne D

N1 - Published online before print September 21, 2015

PY - 2016

Y1 - 2016

N2 - Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers. Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and after 2, 4, 6, 8, and 24 hours for flow cytometry. CD4(+)CD25(+)CD127lowFoxp3(+) regulatory T cells (Tregs), CD4(+)CD161(+) cells, and activated Human leukocyte antigen, HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T-cell cytokine production.

AB - Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers. Peripheral blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and after 2, 4, 6, 8, and 24 hours for flow cytometry. CD4(+)CD25(+)CD127lowFoxp3(+) regulatory T cells (Tregs), CD4(+)CD161(+) cells, and activated Human leukocyte antigen, HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T-cell cytokine production.

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DO - 10.1177/0885066615606673

M3 - Journal article

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SP - 77

EP - 85

JO - Journal of Intensive Care Medicine

JF - Journal of Intensive Care Medicine

SN - 0885-0666

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