INHIBITION OF IL-1 INDUCED TISSUE FACTOR (TF) SYNTHESIS AND PROCOAGULANT ACTIVITY (PCA) IN PURIFIED HUMAN MONOCYTES BY IL-4, IL-10 AND IL-13

Abstract

Exposure of monocytes to pro-inflammatory cytokines or lipopolysaccharide (LPS) may induce synthesis and expression of tissue factor (TF). In this paper we have focused on the induction of TF-activity in human monocytes by the pro-inflammatory cytokines recombinant human (rh) interleukin 1 (rhIL-1α, rhIL-1β)-(rhIL-6) and human tumour necrosis factor alpha (rhTNF-α) measured as procoagulant activity (PCA) in a microtitre plate-based clot assay. In addition we have studied the modulation of IL-1α/β induced TF-mRNA and PCA by rhIL-4, rhIL-10 and rhIL13. IL-1α and IL-1β induced a concentration dependent increase in TF-activity. Neither IL-6 nor TNF-α gave rise to procoagulant activity at the concentrations tested (0.2-20 ng/ml). IL-4, IL-10 and IL-13, all effectively diminished IL-1α/β induced PCA, shown at the protein- and at the mRNA-level, while cell viability was unaffected. These results add to the previously demonstrated role of IL-4 and IL-10 as inhibitors of LPS-induced TF-activity, showing that these anti-inflammatory cytokines are not specific for LPS-activation but interfere with other stimulating substances such as IL-1, which may be involved in diseases where LPS is not present.