The effect of beta‐glucan pretreatment on TNF production in vivo

Abstract

The soluble beta‐glucan preparation PGG‐glucan has been shown to prime antimicrobial functions, including increasing the oxidative burst response, microbicidal activity, and the chemotaxis of leukocytes, without eliciting the production of proinflammatory cytokines. In vitro experiments using primary macrophages and macrophage‐like cell lines have demonstrated that pretreatment with PGG‐glucan can reduce the production of TNF message and protein upon LPS stimulation. The purpose of this study was to examine the effect of PGG‐glucan pretreatment on LPS‐induced TNF protein production in vivo. The hypothesis is that PGG‐glucan pretreatment will result in a reduction of LPS‐induced TNF‐protein levels. To test this hypothesis, CD‐1 mice were pretreated with a single dose of PGG‐glucan 40 hours prior to stimulation with LPS. Following LPS stimulation, serum TNF protein levels were measured by ELISA. Our data suggest that PGG‐glucan pretreatment of mice can attenuate the LPS‐induced TNF production in serum. These results indicate that PGG‐glucan can stimulate cellular immune function while inducing suppression of proinflammatory cytokines in vitro and in vivo. These data and future studies may identify a pharmacological intervention that allows cells of the innate immune system to be primed while not overproducing inflammatory cytokines.Supported by NIHGM66194