Sepsis Research Today is a free monthly online journal that collates and summarizes the latest research about Sepsis, including details on septicemia, diagnosis, symptoms, treatment.

Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice.

Arima H, Motoyama K, Matsukawa A, Nishimoto Y, Hirayama F, Uekama K

Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.

The potential use of hydrophilic cyclodextrins (CyDs) as an inhibitor for lipopolysaccharide (LPS) was examined. Of the five CyDs used in this study, dimethylacetyl-beta-cyclodextrin (DMA7-beta-CyD) had greater inhibitory activity than other CyDs against the production of nitric oxide (NO) and various proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) in murine macrophages stimulated with two serotypes of LPS and lipid A. The inhibitory effect of DMA7-beta-CyD on NO production was also observed in macrophages stimulated with lipoteichoic acid (LTA), but not peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly I:C) or CpG oligonucleotide (CpG-ODN). Several studies have suggested that the inhibitory effects of DMA7-beta-CyD could be ascribed to the interaction with LPS. Simultaneous administration of DMA7-beta-CyD not only intraperitoneally but also intravenously and intraperitoneal injection of aqueous solution containing LPS and d-galactosamine in murine endotoxin shock model suppressed fatality. Also, DMA7-beta-CyD decreased blood level of TNF-alpha as well as serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mice. In conclusion, DMA7-beta-CyD may have promise as a new therapeutic agent for endotoxin shock induced by LPS.

Published 24 October 2005 in Biochem Pharmacol, 70(10): 1506-17.
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