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

Crit Care Med. 2010 Feb;38(2):629-36. doi: 10.1097/CCM.0b013e3181c8fcd0.


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 of the beneficial action of PEGylated drugs may be derived from the anti-inflammatory properties of polyethylene glycol (PEG) itself.

Design: Randomized, double-blinded, controlled ex vivo and in vivo laboratory studies.

Setting: University research laboratories.

Subjects: Human neutrophils and mononuclear cells, macrophage cell line, and adult rats and mice.

Interventions: The effect of PEG (either low-molecular-weight [200-400] or high-molecular-weight [>4000]) was assessed on survival after systemic inflammation induced by lipopolysaccharide or zymosan. The effects of PEG on zymosan, lipopolysaccharide, or streptolysin-induced inflammatory and bioenergetic responses of immune cells were also assessed.

Measurements and main results: Low-molecular-weight PEG reduced inflammatory cytokine expression, pyrexia, and mortality by >50% in both lipopolysaccharide and zymosan models of sepsis. Low-molecular-weight PEG reduced cytokine expression both in vivo and in vitro, and attenuated activation of human neutrophils in response to lipopolysaccharide or zymosan. By contrast, high-molecular-weight PEG conferred less significant survival effects after lipopolysaccharide and zymosan, and it did not exhibit such profound anti-inflammatory effects. Low-molecular-weight PEG attenuated lipopolysaccharide-induced activation of pro-apoptotic pathways (lysophosphatidic acid receptor and caspase-domain signaling) in the livers of endotoxemic rats. Streptolysin-induced necrosis of human neutrophils was reduced by low-molecular-weight PEG, indicating a mechanism that involves coating and/or stabilizing the cellular membrane. Low-molecular-weight PEG preserved human neutrophil responses to septic serum and bioenergetic function in macrophages and neutrophils.

Conclusion: PEG is a commonly used, safe, nonimmunogenic molecule possessing hitherto unappreciated anti-inflammatory properties. Low-molecular-weight PEG may potentially play a role in the therapy of systemic inflammation and sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / biosynthesis
  • Female
  • Flow Cytometry
  • Humans
  • Inflammation / drug therapy
  • Leukocytes, Mononuclear / drug effects
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • Rats
  • Rats, Wistar
  • Sepsis / drug therapy*
  • Stroke Volume / drug effects


  • Anti-Inflammatory Agents
  • Cytokines
  • Polyethylene Glycols