Immune interferon enhances the production of interleukin 1 by human endothelial cells stimulated with lipopolysaccharide

Abstract

Interferon-gamma (IFN-gamma) is a macrophage-activating factor that has also been shown to act on endothelial cells (EC). Interleukin 1 (IL 1), first described as a monocyte product, is also produced by EC after stimulation by lipopolysaccharide (LPS). In this study, the effect of IFN-gamma on the release of IL 1 by EC stimulated with LPS has been investigated. Although IFN-gamma did not stimulate the release of IL 1 or increase the apparent intracellular pool of IL 1 when incubated with EC, there was an increase in the amount of IL 1 released when cells preincubated with IFN-gamma were stimulated with LPS. The effect of IFN-gamma increased with concentration (1 to 1000 U/ml) and with duration of preincubation (24 to 96 hr). The presence of IFN-gamma was not required during the stimulation with LPS. When EC were cultured without IFN-gamma for increasing time periods up to 96 hr, the amount of IL 1 released by EC on subsequent stimulation with LPS progressively decreased. Addition of as little as 1 U/ml of IFN-gamma, however, prevented the loss in capacity of EC to secrete IL 1 when stimulated with LPS. In vivo, EC are involved in the emigration of mononuclear cells from the blood to inflammatory sites. Because IL 1 is chemotactic for lymphocytes and also increases the binding of lymphocytes to EC, activation of EC by T cell-derived factors such as IFN-gamma may augment lymphocyte emigration by increasing the release of IL 1 at the blood-tissue interface.