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  • Title: Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A.
    Author: Visseren F, Verkerk MS, van der Bruggen T, Marx JJ, van Asbeck BS, Diepersloot RJ.
    Journal: Eur J Clin Invest; 2002 Mar; 32 Suppl 1():84-90. PubMed ID: 11886437.
    Abstract:
    BACKGROUND: Chronic low-grade inflammation is associated with increased risk of vascular diseases. The source of inflammation is unknown but may well be chronic and/or repetitive infections with microorganisms. Direct infection of endothelial cells (ECs) may also be a starting point for atherogenesis by initiating endothelial procoagulant activity, increased monocyte adherence and increased cytokine production. We hypothesized that iron-mediated intracellular hydroxyl radical formation after infection is a key event in triggering the production of interleukin-6 (IL-6) by ECs in vitro. METHODS: Cultured ECs were incubated with Fe(II) and Fe(III) or infected with Chlamydia pneumoniae or influenza A/H1N1/Taiwan/1/81 for 48 and 24 h, respectively. To determine the role of iron and reactive oxygen species, cells were coincubated with the H2O2 scavenger N-acetyl-l-cysteine, with the iron chelator deferoxamine (DFO) or with the intracellular hydroxyl radical scavenger dimethylthiourea (DMTU). After the incubation periods, supernatants were harvested for IL-6 determination. RESULTS: Incubating ECs with Fe(II) and Fe(III) resulted in increased IL-6 production. Similarly, infection with C. pneumoniae and influenza A also induced an IL-6 response. Coincubating ECs with DFO or DMTU blocked this response. Nuclear factor-kappaB activity was increased after infection and blocked by coincubation with DFO or DMTU. CONCLUSION: Cultured ECs respond to infection and iron incubation with increased production of IL-6. Iron, the generation of intracellular hydroxyl radical and NF-kappaB activity are essential in cellular activation, suggesting that reactive oxygen species generated in the Haber-Weiss reaction are essential in invoking an immunological response to infection by ECs.
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