Macrophage-activating lipopeptide-2 exerts protective effects in a murine sepsis model.
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.
Zeckey
Christian
C
Trauma Department, Hannover Medical School, Hannover, Germany.
Tschernig
Thomas
T
Hildebrand
Frank
F
Frink
Michael
M
Frömke
Cornelia
C
Dorsch
Martina
M
Krettek
Christian
C
Barkhausen
Tanja
T
D000818:Animals; D002432:Cecum; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000097:blood; D008026:Ligation; D055666:Lipopeptides / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D051195:Toll-Like Receptor 2
D018925:Chemokines; D016207:Cytokines; D055666:Lipopeptides; D051195:Toll-Like Receptor 2; C106335:macrophage stimulatory lipopeptide 2