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Although initially described as an immunomodulatory cytokine, interleukin-10 (IL-10) has also been proposed to exert proinflammatory effects both in vivo and in vitro. In particular, studies in IL-10 transgenic mice have suggested that IL-10 may activate vascular endothelium to promote leucocyte adhesion and extravasation. In the present study we investigated whether IL-10 activates endothelial cells either directly or indirectly, via signals produced by leucocytes in the endothelial cell environment, using a co-culture of human umbilical vein endothelial cells and peripheral blood mononuclear cells (PBMC). No direct effects of IL-10 on endothelial cell responses were observed. However, in the presence of phytohaemagglutinin-activated PBMC, IL-10 increased the expression on endothelial cells of vascular cell adhesion molecule-1 (VCAM-1) but not of intercellular adhesion molecule-1, E-selectin or major histocompatibility complex (MHC) antigens, an effect mediated by PBMC-derived soluble factors. We also observed that interferon-gamma (IFN-gamma) antagonized VCAM-1 expression on endothelial cells mediated by IL-4 and IL-13. Since IL-10 has previously been documented to down-regulate release of IFN-gamma by PBMC, we propose that the IL-10-mediated reduction of IFN-gamma production by PBMC results in enhanced responsiveness of endothelial cells to PBMC-derived IL-4 and IL-13, and thus increased expression of VCAM-1. Our results suggest that the relative balance of cytokines produced by infiltrating cells in developing inflammatory lesions may differentially modulate endothelial responsiveness in vivo, and that IL-10 might indirectly stabilize VCAM-1 expression on endothelial cells by affecting the balance of leucocyte-derived cytokines in the endothelial environment.

Original publication

DOI

10.1046/j.1365-2567.1997.00286.x

Type

Journal article

Journal

Immunology

Publication Date

08/1997

Volume

91

Pages

565 - 571

Addresses

Kennedy Institute of Rheumatology, London, UK.

Keywords

Endothelium, Vascular, Leukocytes, Mononuclear, Humans, Vascular Cell Adhesion Molecule-1, Phytohemagglutinins, Interleukin-4, Interleukin-10, Interleukin-13, Cell Culture Techniques, Cell Communication, Interferon-gamma