Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion

Objective: Monocyte adhesion to endothelial cells and subsequent secretion of matrix metalloproteinases (MMPs) by activated macrophages are key events in arteriosclerosis and restenosis. We tested the hypothesis that interleu kin-10 (IL-10), a potent antiinflammatory cytokine, inhibits monocyte-endot helial cell interactions. Methods: The effect of IL-10 on monocyte/endothel ial cell adhesion, as well as on the expression of MMP-9 and the tissue inh ibitor of MMP-9, TIMP-1, were first tested in vitro in coculture systems. I n addition, we used an ex vivo binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to carotid arteries obtained from either nor mal, or L-nitro arginine-methyl ester (L-NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion molecules (CD18 and CD62-L) wa s studied by flow cytometry. Results: IL-10 (150 ng/ml) inhibits monocyte a dhesion to endothelial cells (by 35%) and to carotid arteries (by 40 and 50 %, in normal and L-NAME-treated rats, respectively), via direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependently decr eases MMP-8 activity and increases TIMP-1 levels in coculture systems, both at the transcriptional level. Conclusions: Our results suggest that IL-10 is an important modulator of monocyte-endothelial cell interactions. (C) 20 01 Elsevier Science B.V. All rights reserved.