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

Abstract

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 TNFα levels following incubation with GM-CSF. The simultaneous incubation with GM-CSF and LPS caused an inhibition of TNFα production (p<0.001). Postincubation with GM-CSF did not yield any difference. In patients, preincubation with GM-CSF yielded an enhanced ex vivo TNFα-response when TNFα levels were low. Patients with increased TNFα concentrations 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 TNFα may represent endotoxin tolerance.