Granulocyte colony-stimulating factor (G-CSF) has immunomodulating properties that could be beneficial for adjunctive treatment of severe infections. Cytokine release from stimulated whole blood and expression of neutrophil surface and apoptosis markers in response to G-CSF were studied in human volunteers under physiologic conditions and after ethanol pretreatment. Levels of interleukin (IL)-1 receptor antagonist and soluble tumor necrosis factor (TNF) receptor-1 were significantly increased after G-CSF, whereas TNF-alpha and IL-10 concentrations were reduced, and IL-1beta and IL-8 remained unchanged. There was a significant inhibition of neutrophil apoptosis and increased expression of complement regulatory protein CD55 without changes in CD11b, CD14, and CD59 expression. These effects were well preserved after ethanol pretreatment, which per se led to an increase in apoptosis and decreased CD55 expression. Thus, G-CSF treatment was associated with a reduction of the proinflammatory cytokine response and enhanced neutrophil survival in vivo, suggesting a therapeutic potential of G-CSF for severe infections in the nonneutropenic host.