Comparison of the potency of a variety of β-glucans to induce cytokine production in human whole blood

beta-Glucans are components of fungal cell walls and potent stimulants of innate immunity. The majority of research on biological activities of glucans has focused on beta-(1 -> 3)-glucans, which have been implicated in relation to fungal exposure-associated respiratory symptoms and as important stimulatory agents in anti-fungal immune responses. Fungi-and bacteria and plants-produce a wide variety of glucans with vast differences in the proportion and arrangement of their beta-(1 -> 3)-, -(1 -> 4)- and -(1 -> 6)-glycosidic linkages. Thus far, the pro-inflammatory potential of different beta-glucans has not been studied within the same experimental model. Therefore, we compared the potency of 13 different glucan preparations to induce in vitro production of IL-1 beta, IL-6, IL-8 and TNF-alpha in human, whole blood cultures. The strongest inducers of all cytokines were pustulan [beta-(1 -> 6)-glucan], lichenan [beta-(1 -> 3)-(1 -> 4)-glucan], xyloglucan [beta-(1 -> 4)-glucan] and pullulan [alpha-(1 -> 4)-(1 -> 6)-glucan]. Moderate-to-strong cytokine production was observed for curdlan [beta-(1 -> 3)-glucan], baker's yeast glucan [beta-(1 -> 3)-(1 -> 6)-glucan] and barley glucan [beta-(1 -> 3)-(1 -> 4)-glucan], while all other glucan preparations induced very low, or no, detectable levels of cytokines. We therefore conclude that innate immunity reactions are not exclusively induced by beta-(1 -> 3)-glucans, but also by beta-(1 -> 6)- and beta-(1 -> 4)-structures. Thus, not only beta-(1 -> 3)-glucan, but also other beta-glucans and particularly beta-(1 -> 6)-glucans should be considered in future research.