Background and Goal of Study:
Daptomycin is a lipopeptide antibiotic used in the treatment of systemic and lifethreatening infections caused by Grampositive organisms.It has a particular
mechanism of action, disrupting multiple aspects of bacterial cell membrane function, w hich makes it useful in treating infections caused by multiple drugresistant bacteria. In addition to its antibacterial properties, there is also some evidence indicating that it could also exhibit antiinflammatory and
immunomodulatory effects beneficial in the treatment of infections. Using an in vitro approach, our study pretends to explore how daptomycin administration modulates endothelial cell response to TNFα stimulation.
Materials and Methods:
Primary human endothelial cells (HUVECs) were stimulated with TNFα (15 μg/mL) for 18h and subsequently treated w ith daptomycin (0: control group, 15, 25, 50 or 100 μg/mL). The tested doses are within the therapeutic plasmatic concentrations for daptomycin.Samples were taken 24h after daptomycin treatment to measure cell necrosis (lactate dehydrogenase release) and levels of proinflammatory
interleukin (IL6), the chemokine monocyte chemoattractant protein 1 (MCP1)
and the adhesion molecule Eselectin.
After the normality of data were assessed by Kolmogorov Smirnov test, statistical analysis w as performed with ANOVA followed by post hoc test when appropriate using statistical software Prism 5 (GraphPad). A p< 0.05 was considered statistically significant.
Results and discussion:
All tested doses of daptomycin protected against TNFα induced endothelial cell necrosis (all p< 0.05). A dose of 25 μg/mL or greater reduced levels of IL6 as well as levels of MCP1 and Eselectin (all p< 0.05). Treatment of HUVECs with the 15 μg/mL dose did not show effects on the levels of the analyzed mediators (all p≥0.05). Maximum reduction of IL6, MCP1 and Eselectin levels was observed in the 50 μg/mL group, without differences respect to results observed with 100 μg/mL group (all p≥0.05).
Conclusion(s): 
Daptomycin has shown protective effects against human endothelial cell death
induced by TNFα.
Our results also suggest that this effect might be related to an attenuation of
inflammatory, chemotactic and cell adhesion mechanisms. Future studies might explore the potential role of daptomycin in modulating molecular mechanisms involved in inflammatory processes, expanding its beneficial role besides its known antimicrobial effect.

Effects of daptomycin treatment on TNF-&#945;-stimulated human endothelial cells

Effects of daptomycin treatment on TNF-α-stimulated human endothelial cells