Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men

We investigated the effects of granulocyte colony‐stimulating factor (G‐CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. Twelve hours before both experiments, 10 of these subjects were pretreated with 300 micrograms G‐CSF subcutaneously. G‐CSF itself increased granulocyte and monocyte counts and the plasma levels of tumor necrosis factor‐alpha (TNF‐alpha), soluble TNF receptors (sTNF‐R) p55, and p75 and interleukin‐1 receptor antagonist (IL‐1ra). G‐CSF did not influence plasma IL‐1 beta and IL‐6 levels. In the G‐CSF‐pretreated subjects endotoxin‐induced surges in rectal temperature and in the plasma levels of TNF‐alpha plasma levels were about 50% increased, and surges in the plasma levels of both sTNF‐Rs and IL‐1ra were about twice as high as in the control group. Endotoxin‐induced increases in IL‐6, cortisol, and heart rate were not modified by G‐CSF pretreatment. Endotoxin administration induced a transient 50% reduction in leukocyte counts in the G‐CSF‐pretreated subjects that was not seen in the control group. We conclude that a single stand dose of G‐CSF increases the plasma levels of cytokines and cytokine receptors and considerably modifies the host response of healthy humans to a low dose of endotoxin.