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 v ivo host response to Salmonella abortus equi endotoxin in healthy male s, Twenty volunteers received 0.8 ng/kg endotoxin and saline intraveno usly 1 week apart in randomized order. Twelve hours before both experi ments, 10 of these subjects were pretreated with 300 mu g G-CSF subcut aneously. G-CSF itself increased granulocyte and monocyte counts and t he plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble T NF receptors (sTNF-R) p55, and p75 and interleukin-1 receptor antagoni st (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 t emperature and in the plasma levels of TNF-alpha plasma levels were ab out 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-in duced 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 wa s not seen in the control group, We conclude that a single standard do se of G-CSF increases the plasma levels of cytokines and cytokine rece ptors and considerably modifies the host response of healthy humans to a low dose of endotoxin. (C) 1996 by The American Society of Hematolo gy.