Low-molecular-weight polyethylene glycol improves survival in experimental sepsis*

• DOI: 10.1097/ccm.0b013e3181c8fcd0
• Publication Date: 2010-01-14T07:51:53Z
• Authors: Gareth L. Ackland; Ana Gutierrez Del...; Song T. Yao; Robert C. Stephens; Alexander Dyson; Nigel J. Klein; Mervyn Singer; Alexander V. Gourine
• Keywords: Zymosan

Objective: For several chronic inflammatory disease states, therapy is enhanced by improving the pharmacokinetic properties of anti-inflammatory drugs through conjugation with polyethylene glycol. We hypothesized that part beneficial action PEGylated may be derived from glycol (PEG) itself. Design: Randomized, double-blinded, controlled ex vivo and in laboratory studies. Setting: University research laboratories. Subjects: Human neutrophils mononuclear cells, macrophage cell line, adult rats mice. Interventions: The effect PEG (either low-molecular-weight [200–400] or high-molecular-weight [>4000]) was assessed on survival after systemic inflammation induced lipopolysaccharide zymosan. effects zymosan, lipopolysaccharide, streptolysin-induced bioenergetic responses immune cells were also assessed. Measurements Main Results: Low-molecular-weight reduced cytokine expression, pyrexia, mortality >50% both zymosan models sepsis. expression vitro, attenuated activation human response to By contrast, conferred less significant it did not exhibit such profound effects. lipopolysaccharide-induced pro-apoptotic pathways (lysophosphatidic acid receptor caspase-domain signaling) livers endotoxemic rats. Streptolysin-induced necrosis PEG, indicating a mechanism involves coating and/or stabilizing cellular membrane. preserved neutrophil septic serum function macrophages neutrophils. Conclusion: commonly used, safe, nonimmunogenic molecule possessing hitherto unappreciated properties. potentially play role