Inhibition of intracellular tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 production in human monocytes by iloprost.

Abstract

To investigate the effects of iloprost as a stable prostacyclin analogue on intracellular expression of IL-6 and TNF-alpha of lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system assessed by flow cytometry. Whole blood of six healthy volunteers processed immediately after withdrawal and twice on different days (six measurements per experiment) was stimulated in two different settings with LPS (final concentrations 0.2 ng mL(-1) and 10 ng mL(-1)) and incubated with iloprost (final concentrations in each experiment were 0.01 nm, 0.1 nm, 0.3 nm, 1 nm, 3 nm, 10 nm, 30 nm and 100 nm) for 3 h at 37 degrees C and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry. Our investigations showed, for the first time, that iloprost (0.1 nm up to 100 nm) caused a dose-dependent inhibitory effect of IL-6 production in human monocytes stimulated with LPS (10 ng mL(-1)), which was even more obvious in monocytes stimulated with lower concentrated LPS (0.2 ng mL(-1)). Iloprost (0.1 nm up to 100 nm) was found to inhibit TNF-alpha production of LPS-stimulated monocytes in a dose-dependent fashion not influenced by LPS concentration. Apart from the vasodilatory and antithrombotic effects, iloprost may also down-regulate the intracellular expression of IL-6 and TNF-alpha in human monocytes.