Macrophage-activating lipopeptide-2 exerts protective effects in a murine sepsis model

Shock. 2010 Jun;33(6):614-9. doi: 10.1097/SHK.0b013e3181cb8db4.


It is still a major problem to achieve successful therapy in polymicrobial sepsis. Stimulation of the innate immune system via Toll-like receptors (TLRs) 2 and 6 had beneficial effects on chronic inflammatory disorders and a severe peritonitis model when administered 4 days before induction. In the present study, the hypothesis whether the TLR-2 and TLR-6 pathway can also be used as a therapeutic agent parallel to sepsis induction and several hours after the induction was tested. Therefore, the TLR-2 and TLR-6 agonist macrophage-activating lipopeptide 2 (MALP-2) was applied simultaneous to cecal ligation and puncture-sepsis induction and 6 h thereafter. Vehicle-treated animals served as controls. Survival, activity, cytokine levels at different time points, and pulmonary neutrophil infiltration were determined. Improved survival was found after both MALP-2 treatments in comparison with untreated controls. The treatment resulted in reduced monocyte chemotactic protein 1 levels in the plasma; furthermore, pulmonary infiltration by neutrophils was decreased. These results demonstrate a beneficial effect of MALP-2 as a therapeutic agent in polymicrobial sepsis in the cecal ligation and puncture mouse model.

MeSH terms

  • Animals
  • Cecum
  • Chemokines / immunology
  • Cytokines / blood
  • Ligation
  • Lipopeptides / therapeutic use*
  • Lung / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology
  • Peritonitis / immunology
  • Sepsis / immunology
  • Sepsis / mortality
  • Sepsis / prevention & control*
  • Toll-Like Receptor 2


  • Chemokines
  • Cytokines
  • Lipopeptides
  • Toll-Like Receptor 2
  • macrophage stimulatory lipopeptide 2