BJA Advance Access originally published online on October 28, 2009
British Journal of Anaesthesia 2009 103(6):833-839; doi:10.1093/bja/aep298
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Regulation of pentraxin-3 by antioxidants
1 Academic Unit of Anaesthesia and Intensive Care, School of Medicine and Dentistry and
2 Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, UK
* Corresponding author. E-mail: h.f.galley{at}abdn.ac.uk
Background: Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its regulatory mechanisms are still unclear. Oxidative stress is well defined in patients with sepsis and has a role in regulation of inflammatory pathways which may include PTX3. We undertook an in vitro study of the effect of antioxidants on regulation of PTX3 in endothelial cells combined with a prospective observational pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative stress in patients with sepsis.
Methods: Human endothelial cells were cultured with lipopolysaccharide 2 µg ml–1, peptidoglycan G 20 µg ml–1, tumour necrosis factor (TNF) 
10 ng ml–1, interleukin-1 (IL-1) β 20 ng ml–1, or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 µM. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.
Results: PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1–202) ng ml–1 compared with 6 (1–12) ng ml–1, P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1–1.7) mM compared with 2.2 (1.3–3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3–10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF plus IL-1β. PTX3 concentrations were lower in cells co-treated with antioxidants (all P<0.05), associated with lower nuclear factor 
B expression for NAC and trolox (P<0.05).
Conclusions: PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.
Keywords: immune response; infection, bacterial; infection, fungal; metabolism, protein, acute phase