A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock

Abstract

Capsular material of the opportunistic fungusCryptococcus neoformansis composed mainly of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in anin vivoexperimental system of lipopolysaccharide (LPS)-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS fromEscherichia coli. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6, whereas mice that were also treated with GXM showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IκBα activation. Importantly, the inhibitory effect of GXM on proinflammatory cytokine secretion was reproduced by treatment with wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in the rate of survival by dampening the hyperinflammatory response.