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.
Pollmächer
T
T
Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Germany.
Korth
C
C
Mullington
J
J
Schreiber
W
W
Sauer
J
J
Vedder
H
H
Galanos
C
C
Holsboer
F
F
D001427:Bacterial Toxins / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000009:adverse effects*; D005334:Fever / Q000139:chemically induced; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D018121:Receptors, Cytokine / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D012772:Shock, Septic / Q000139:chemically induced / Q000517:prevention & control*; D012795:Sialoglycoproteins / Q000032:analysis; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001427:Bacterial Toxins; D016207:Cytokines; D004731:Endotoxins; C507763:IL1RN protein, human; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins; D018121:Receptors, Cytokine; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C027952:salmonella toxin; D016179:Granulocyte Colony-Stimulating Factor; D006854:Hydrocortisone