Interleukin 10 regulates cellular responses in monocyte/endothelial cell co-cultures.

Adhesive interactions between monocytes and vascular endothelial cells increase the expression of the inflammatory genes, tissue factor (TF) and E-selectin, thus contributing to the inflammatory process. In this study, we have shown that these responses could be regulated by the immunomodulatory cytokine interleukin 10 (IL-10). IL-10 reduced TF generation in monocyte/endothelium co-cultures (64. 3 +/- 3.3% reduction, P < 0.01, n = 4) by acting directly on monocytes, whereas IL-4 inhibited TF expression in both monocytes and endothelium. Similarly, IL-10 reduced the induction of endothelial E-selectin by monocytes (100% reduction at 21 h), but had no effect on cytokine-induced E-selectin expression. IL-10 itself was not able to induce E-selectin protein or mRNA in endothelial cells. IL-10 mRNA was detected in monocytes after 6 h co-culture with endothelial cells, and was sustained for up to 30 h. Finally, IL-10 significantly reduced the adhesion of monocytes to endothelium (45% reduction), which may account in part for the inhibitory actions of IL-10. We conclude that IL-10 has an anti-inflammatory effect on monocyte/endothelium interactions, and may itself be produced as a result of such interactions.