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

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 - © The Author(s) 2015.

PY - 2017/1/1

Y1 - 2017/1/1

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-3 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-3 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.

U2 - 10.1177/0885066615606673

DO - 10.1177/0885066615606673

M3 - Journal article

C2 - 26392625

SN - 0342-4642

VL - 32

SP - 77

EP - 85

JO - Intensive Care Medicine

JF - Intensive Care Medicine

IS - 1

ER -