Granulocyte colony-stimulating factor (G-CSF) is an important regulator of
granulopoiesis and an inducer of T helper 2 (Th2)-related cytokines. In thi
s study we investigated the mechanism of cytokine-modulated G-CSF productio
n in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells
(PBMC) and bone marrow stromal cells (BMSC). In PBMC, LPS significantly in
duced G-CSF and interleukin (IL)-1, an inducer of G-CSF. Both were partly i
nhibited by IL-4, IL-6 and IL-10. None of these effects were the result of
altered monocyte activation or proliferation. The effects of IL-4 and IL-10
appeared to be independent of IL-l suppression or IL-1 receptor antagonist
(IL-1ra) induction, but rather seemed to involve a blockade of IL-l functi
on, in addition to a blockade of IL-l-independent stimulatory effects on G-
CSF production. The effect of the IL-6-induced suppression of G-CSF product
ion differed from that of IL-4 and IL-10 in that it was much less pronounce
d and could be partially overridden by addition of functional IL-1, yet it
also appeared to involve the interference with IL-1 function and the suppre
ssion of TL-l-independent mechanisms. In BMSC, G-CSF synthesis was regulate
d differently. Here, IL-I was the main stimulator of G-CSF release, and the
effect of IL-1 was neither affected by IL-10 nor IL-6, while IL-4 had a st
imulatory effect. Thus, G-CSF production was found to be differently regula
ted in distinct cellular compartments, and a cross-regulation between these
might be facilitated by IL-4-, IL-6- and IL-10-induced inhibition of IL-l.
These results could be important for the understanding of G-CSF production
in neutropenic patients during severe infection.