Effects of the Linear Fragments of Beta-(1→3)-Glucans on Cytokine Production in vitro

Abstract

Beta-glucans, homopolysaccharides composed of 3,6-branching β-(1→3)-D-glucan chains, attract great interest as inducers of cytokine synthesis. In this work, we studied the ability of linear fragments of beta-glucan chains to activate cytokine synthesis. Synthetic nona-β-(1→3)-D-glucoside (SO) representing a linear fragment of beta-glucan chain, endotoxin (ED), and natural β-(1→3)-D-glucan (GL) were tested for their role as inducers of cytokines in whole peripheral blood cultures collected from 17 individuals. The concentrations of IL-12p70, IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF-α, and TNF-β were measured in the supernatants after 2, 24, and 48 h of cell culturing. SO, ED, and GL stimulated production of pro-inflammatory IFN-γ, IL-1β, IL-2, IL-6, IL-8, TNF-α and anti-inflammatory IL-10. The highest levels of biosynthesis after stimulation with SO were registered for IL-6, IL-8, and TNF-α. SO stimulated production of all cytokines (except IFN-γ) to a lesser extent than ED and GL. The IFN-γ/IL-10 (Th1/Th2) ratios after 24 and 48 h of culturing were 3.1 and 7.5 for SO; 0.03 and 0.1 for GL; and 0.06 and 0.2 for ED, respectively. The results indicate that linear fragments of beta-glucans cause a more pronounced shift of immune response towards the pro-inflammatory (Th1) type than beta-glucan itself.

Detection of Beta-Glucan Contamination in Nanotechnology-Based Formulations

“…Pro-inflammatory cytokines TNFα, IL-1β, IL-6, and IL-8 were reported as biomarkers of the beta-glucan-mediated pro-inflammatory response in human blood [ 20 ]. This observation is consistent with another study that also observed TNFα, IL-6, and IL-8 in whole blood cultures of healthy donors treated in vitro with yeast and synthetic β-(1,3)-glucans [ 21 ]. Interestingly, this study also demonstrated that linear fragments of beta-glucans were more potent at inducing Th1 responses in human blood cells in vitro than full-size molecules [ 21 ].…”

“…This observation is consistent with another study that also observed TNFα, IL-6, and IL-8 in whole blood cultures of healthy donors treated in vitro with yeast and synthetic β-(1,3)-glucans [ 21 ]. Interestingly, this study also demonstrated that linear fragments of beta-glucans were more potent at inducing Th1 responses in human blood cells in vitro than full-size molecules [ 21 ]. Another interesting observation is that synthetic beta-glucans were weaker immunostimulants than their naturally derived counterparts [ 21 ].…”

“…Interestingly, this study also demonstrated that linear fragments of beta-glucans were more potent at inducing Th1 responses in human blood cells in vitro than full-size molecules [ 21 ]. Another interesting observation is that synthetic beta-glucans were weaker immunostimulants than their naturally derived counterparts [ 21 ]. Even though the authors conducted experiments to rule out the potential contribution of endotoxin contamination to the cytokine response [ 21 ], it is not improbable that other undetected IIMIs present in the naturally-derived beta glucans contributed to their higher potency.…”

“…Another interesting observation is that synthetic beta-glucans were weaker immunostimulants than their naturally derived counterparts [ 21 ]. Even though the authors conducted experiments to rule out the potential contribution of endotoxin contamination to the cytokine response [ 21 ], it is not improbable that other undetected IIMIs present in the naturally-derived beta glucans contributed to their higher potency. Other examples demonstrating the structure activity relationships of beta glucans in different species both in vitro and in vivo are summarized in Table 1 .…”

Variants of Mitochondrial Genome and Risk of Multiple Sclerosis Development in Russians

“…To date, there have been approximately 20 studies devoted to the analysis of the association between MS and mitochondrial genome variants: both individual polymorphisms and haplogroups, with the samples being relatively small in some of the cases (see references in review [7]). Among these works, two studies were performed using the GWAS method, and the others involved the “candidate gene” approach.…”