Fig. 3.
SCH 14988 specifically induces G-CSF from LPS-stimulated human blood monocytes. Human PBMNs were cultured with 0.1 ng/mL LPS in the presence of varying concentrations of SCH 14988 or vehicle (0.1% DMSO). Data, expressed as percent of control, are normalized to the LPS plus vehicle (0 μmol/L SCH 14988) value, which was arbitrarily set at 100%. Each data point represents at least 6 donors. Absolute levels of each cytokine (in pg/mL) in the LPS plus vehicle group were IL-1β, 3,075 ± 417; IL-6, 4,800 ± 1,300; TNFα, 1,093 ± 245; and G-CSF, 1,088 ± 345. G-CSF levels were 2,721 ± 467 pg/mL in cultures treated with LPS plus 25 μmol/L SCH 14988. This enhancement of G-CSF production was statistically significant, as judged by the Students' t-test (P < .01). Cytokine levels were always less than 70 pg/mL in unstimulated cultures. In addition, in eight separate experiments, steady-state G-CSF mRNA levels (determined as described in Fig 2) in elutriated monocytes treated with LPS (0.1 ng/mL) plus SCH 14988 (25 μmol/L) were enhanced by threefold compared with monocytes treated with LPS alone.