IL-10 INHIBITS PROSTAGLANDIN E(2) PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED MONOCYTES

Since IL-10 has recently been shown to exhibit pleiotropic effects on human monocytes, it was of interest to determine the effect of this cytokine on prostaglandin E(2) (PGE(2)) production by monocytes. Recombinant IL-10 (rIL-10) did not significantly affect PGE(2) production by lipopolysaccharide (LPS)-unstimulated monocytes, but efficiently inhibited PGE(2) production by LPS-stimulated monocytes. The inhibition by rIL-10 was achieved in a dose-dependent manner. Recombinant IL-4 also inhibited PGE(2) production at the same degree as rIL-10. Viral IL-10 inhibited PGE(2) production by monocytes in a similar fashion as did human rIL-10. Endogenously produced IL-10 was also shown to inhibit PGE(2) production by LPS-stimulated monocytes. Kinetic studies showed that the inhibition by rIL-10 on PGE(2) production was observed at least 3 h after LPS stimulation. Taken together, these results indicate that IL-10 may play an important role in modulating immunological responses via down-regulation of PGE(2) production by monocytes.