Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity

Franz Josef Neumann, Ilka Ott, Nikolaus Marx, Thomas Luther, Silke Kenngott, Meinrad Gawaz, Mathias Kotzsch, Albert Schömig

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263 Scopus citations

Abstract

Interleukin (IL)-6 and IL-8 are important regulators of inflammatory responses 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 investigated the effect of IL-6 and IL-8 on monocyte tissue factor (TF) expression. Recombinant human IL-6 and IL-8 caused a time- and dose-dependent increase in PCA (recalcification time) of monocytic U937 cells and of mononuclear leukocytes. Using blocking anti-TF monoclonal antibodies and factor VII- deficient control plasma, this PCA was shown to be TF dependent. Compared with unstimulated cells, mononuclear cell PCA increased by 4.5-fold to 17±2 mU/5 x 105 cells after exposure to 100 ng/L IL-6 for 4 hours and by 6.6- fold to 27±4 mU/5 x 105 cells after exposure to IL-8 under the same conditions. Northern blot analysis showed 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 was 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.

Original languageEnglish
Pages (from-to)3399-3405
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number12
DOIs
StatePublished - 1997

Keywords

  • Interleukins
  • Monocytes
  • Tissue factor

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