Inhibition of human monocyte adhesion by interleukin-4

Abstract

The adhesion of monocytes to vascular surfaces is central to inflammation and atherogenesis; however, very little is known about regulatory factors that can prevent these processes. Here we report the inhibition of human monocyte adhesion to human endothelial layers and plastic by interleukin-4 (IL-4), a T-cell-derived glycoprotein with pleiotropic activities. The inhibitory effects of IL-4 were seen with basal and cytokine-stimulated monocyte adhesion, were apparent at low concentration, and were abolished by inactivating IL-4. No direct toxic effect of IL-4 on monocytes was detected. Inhibition of adhesion was accompanied by small increases in monocyte surface expression of the leukocyte-functional antigen group of adhesion structures, suggesting that absolute levels of expression may be less important than the functional status of such molecules in the regulation of monocyte adhesion. In addition, inhibition by IL-4 of cytokine-stimulated monocyte adhesion was not associated with changes in the surface expression of cytokine receptors. These results suggest a role for IL-4 in the regulation of monocyte adhesion, and may provide for a common mechanism for the inhibitory effects of IL-4 on monocyte function.

Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia

“…Fresh CM was added into the wells and the glass‐ or plastic‐adherent MNCs were further incubated in 1 ml CM at 37°C with 5% CO 2 with or without cytokines for 1–4 days. No significant changes in the number of MNCs adhering on glass due to IL‐4 (up to 10 ng ml −1 ) were observed as has been reported for adherence on plastic surfaces [19].…”

“…It has been found to inhibit production of IL‐1 [7, 8], tumor necrosis factor‐α (TNFα) [9, 10], granulocyte colony‐stimulating factor (G‐CSF), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) [11], IL‐6 [12–15]and IL‐8 [16], as well as activation of macrophages by interferon‐γ (IFN‐γ), IL‐1, TNFα and GM‐CSF, resulting in a suppression of oxidative burst and intracellular killing [17, 18]. IL‐4 also has been shown to suppress adhesion [19], expression of CD14 [20]and monocyte‐mediated cytotoxicity [21]as well as nitric oxide production and antifungal activity of murine macrophages [22].…”

Lymphocyte Activation as a Possible Measure of Atherosclerotic Risk in Patients with Sleep Apnea

“…Furthermore, catecholamines, which have been shown to be increased in OSA patients,44 have also been shown to inhibit the production of type 1 cytokines by T cells and to stimulate the production of type 2 cytokines such as IL‐4 and IL‐10, possibly through stimulation of the β 2 ‐adrenoreceptor‐cAMP‐protein kinase A pathway 45. The shift towards type 2 dominance may represent a protective mechanism in OSA to attenuate or moderate hypoxia‐induced atherogenesis by increasing IL‐4 production, as IL‐4 has also been shown to possess antiatherogenic properties46,47 via suppression of proinflammatory cytokine production. It should be noted, however, that IL‐4 has also been reported to possess proatherogenic properties, particularly in the early stages of the disease 19.…”

Regulation of the uPAR/uPA system expressed on monocytes by the deactivating cytokines, IL‐4, IL‐10 and IL‐13: consequences on cell adhesion to vitronectin and fibrinogen

“…In particular, they prevent the generation of tissue factor on LPS‐activated monocytes ( Ramani et al , 1993 ; Herbert et al , 1993 ) and down‐regulate fibrinogen biosynthesis ( Vasse et al , 1996 ). Furthermore, IL‐4 and IL‐10 inhibit both adhesion of monocytes to endothelial cells ( Elliot et al , 1991; Krakauer, 1995) and in vivo production of superoxide anions ( Gazinelli et al , 1992 ; Herbert et al , 1993 ). In addition, it has been found that IL‐10 is also expressed in advanced atherosclerotic lesions but not in normal vessels ( Uyemura et al , 1996 ).…”