The Effects of Ex Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Endotoxin on Cytokine Release of Whole Blood Are Determined by Priming Conditions
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The Effects of Ex Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Endotoxin on Cytokine Release of Whole Blood Are Determined by Priming Conditions. / Nierhaus, A; Linssen, J; Winkler, M S; Frings, D P; Kluge, S.
In: BIOMED RES INT , Vol. 2017, 2017, p. 9834512.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The Effects of Ex Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Endotoxin on Cytokine Release of Whole Blood Are Determined by Priming Conditions
AU - Nierhaus, A
AU - Linssen, J
AU - Winkler, M S
AU - Frings, D P
AU - Kluge, S
PY - 2017
Y1 - 2017
N2 - Background: Lipopolysaccharide- (LPS-) induced tumour necrosis factor alpha (TNFα) secretion in critically ill patients can be considered as a measure of immune responsiveness. It can be enhanced by granulocyte-macrophage colony stimulating factor (GM-CSF). We investigated the effect of GM-CSF on ex vivo stimulated cytokine production using various preincubation regimens in healthy donors and patients with sepsis.Results: The maxima for the stimuli occurred 3 hours after stimulation. In donors, there was an increase (p< 0.001) of LPS-induced TNFαlevels following incubation with GM-CSF. Thesimultaneousincubation with GM-CSF and LPS caused an inhibition of TNFαproduction (p< 0.001).Postincubationwith GM-CSF did not yield any difference. In patients, preincubation with GM-CSF yielded an enhanced ex vivo TNFα-response when TNFαlevels were low. Patients with increased TNFαconcentrations did not show a GM-CSF stimulation effect. The GM-CSF preincubation yielded an increase of IL-8 production in patients and donors.Conclusions: This study demonstrates the immune-modulating properties of GM-CSF depending on the absence or presence of LPS or systemic TNFα. The timing of GM-CSF administration may be relevant for the modulation of the immune system in sepsis. The lack of stimulation in patients with high TNFαmay represent endotoxin tolerance.
AB - Background: Lipopolysaccharide- (LPS-) induced tumour necrosis factor alpha (TNFα) secretion in critically ill patients can be considered as a measure of immune responsiveness. It can be enhanced by granulocyte-macrophage colony stimulating factor (GM-CSF). We investigated the effect of GM-CSF on ex vivo stimulated cytokine production using various preincubation regimens in healthy donors and patients with sepsis.Results: The maxima for the stimuli occurred 3 hours after stimulation. In donors, there was an increase (p< 0.001) of LPS-induced TNFαlevels following incubation with GM-CSF. Thesimultaneousincubation with GM-CSF and LPS caused an inhibition of TNFαproduction (p< 0.001).Postincubationwith GM-CSF did not yield any difference. In patients, preincubation with GM-CSF yielded an enhanced ex vivo TNFα-response when TNFαlevels were low. Patients with increased TNFαconcentrations did not show a GM-CSF stimulation effect. The GM-CSF preincubation yielded an increase of IL-8 production in patients and donors.Conclusions: This study demonstrates the immune-modulating properties of GM-CSF depending on the absence or presence of LPS or systemic TNFα. The timing of GM-CSF administration may be relevant for the modulation of the immune system in sepsis. The lack of stimulation in patients with high TNFαmay represent endotoxin tolerance.
KW - Journal Article
U2 - 10.1155/2017/9834512
DO - 10.1155/2017/9834512
M3 - SCORING: Journal article
C2 - 29387728
VL - 2017
SP - 9834512
JO - BIOMED RES INT
JF - BIOMED RES INT
SN - 2314-6133
ER -
