Eukaryotic translation initiation factor 5A small interference RNA-liposome complexes reduce inflammation and increase survival in murine models of severe sepsis …
CC Moore, EN Martin, G Lee, C Taylor… - Journal of Infectious …, 2008 - academic.oup.com
CC Moore, EN Martin, G Lee, C Taylor, R Dondero, LL Reznikov, C Dinarello, J Thompson…
Journal of Infectious Diseases, 2008•academic.oup.comBackground. Many novel therapeutics have failed to reduce all-cause mortality associated
with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of
apoptosis as well as inflammatory cell activation, making it a potential target for sepsis
therapy. Methods. In a murine model of severe sepsis, mice were intraperitoneally
challenged with lipopolysaccharide (LPS). Mice were treated both before and after LPS
challenge with liposome complexes containing either an eIF5Aspecific or control small …
with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of
apoptosis as well as inflammatory cell activation, making it a potential target for sepsis
therapy. Methods. In a murine model of severe sepsis, mice were intraperitoneally
challenged with lipopolysaccharide (LPS). Mice were treated both before and after LPS
challenge with liposome complexes containing either an eIF5Aspecific or control small …
Abstract
Background. Many novel therapeutics have failed to reduce all-cause mortality associated with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of apoptosis as well as inflammatory cell activation, making it a potential target for sepsis therapy.
Methods. In a murine model of severe sepsis, mice were intraperitoneally challenged with lipopolysaccharide (LPS). Mice were treated both before and after LPS challenge with liposome complexes containing either an eIF5Aspecific or control small interference RNA (siRNA), and both survival and serum concentrations of inflammatory cytokines were monitored. The ability of eIF5A siRNA to reduce inflammatory cytokines was also tested in a model of acute lung injury established by intranasal administration of LPS to mice.
Results. There was a statistically significant increase in the rate of survival for mice intraperitoneally challenged with LPS that received eIF5A siRNA, compared with that noted for mice that received control siRNA (71% vs. 5%; P < .001), as well as a reduction in cytokine expression in serum. Concentrations of proinflammatory cytokines were also reduced in the lung homogenates and serum of mice that were intranasally challenged with LPS and received eIF5A siRNA (P ⩽ .05).
Conclusions. eIF5A siRNA-liposome complexes reduced inflammation and contributed to increased survival in a model of severe sepsis, decreased inflammation in a model of acute lung injury, and should be considered for clinical use.
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