EFFECT OF HUMAN RECOMBINANT INTERLEUKIN-6 AND INTERLEUKIN-8 ON MONOCYTE PROCOAGULANT ACTIVITY

Interleukin (IL)-6 and IL-8 are important regulators of inflammatory r esponses in myocardial infarction. Induction of monocyte procoagulant activity (PCA) by these cytokines could present a mechanism that links inflammatory responses to thrombotic events. We therefore investigate d the effect of IL-6 and IL-8 on monocyte tissue factor (TF) expressio n. Recombinant human IL-6 and IL-8 caused a time- and dose-dependent i ncrease in PCA (recalcification time) of monocytic U937 cells and of m ononuclear leukocytes. Using blocking anti-TF monoclonal antibodies an d factor VII-deficient control plasma, this PCA was shown to be TF dep endent. Compared with unstimulated cells. mononuclear cell PCA increas ed by 4.5-fold to 17+/-2 mU/5 x 10-(5) cells after exposure to 100 ng/ L IL-6 for 4 hours and by 6.6-fold to 27+/-4 mU/5 x 10(5) cells after exposure to IL-8 under the same conditions. Northern blot analysis sho wed an increase in TF mRNA after stimulation with IL-6 or IL-8 for 2, hours, and after 4 hours an increase in cellular TF protein content wa s found by immunoassay. Flow cytometry demonstrated that IL-6 and IL-8 induced an increase in TF surface expression on monocytes. Thus, IL-6 and IL-8 induce monocyte PCA by increasing mRNA, protein content, and surface expression of TF.