Soluble
beta-1,3-glucan has been demonstrated to protect against
infection and
shock in rats and mice, and clinical studies suggest that administration of soluble
glucans to
trauma/surgical patients decreases septic complications and improves survival. However, little is known about the precise mechanisms by which
glucans influence the state of activation of blood cells, which are responsible for the fulminant
cytokine production and the activation of the coagulation system observed in serious gram-negative
infection. We studied therefore the effect of an underivatized, soluble yeast
beta-1,3-glucan and
lipopolysaccharide (LPS), either alone or in combination, on
tumor necrosis factor-alpha (
TNFalpha),
interleukin-6 (IL-6),
IL-8 and
IL-10 secretion and monocyte
tissue factor (TF) expression in human whole blood. As expected, LPS induced the secretion of substantial amounts of all measured parameters, whereas only minor amounts of
TNFalpha,
IL-6, and
IL-10 were induced by
beta-glucan itself. However,
beta-glucan itself induced the production of significant amounts of
IL-8 and TF. Soluble
beta-1,3-glucan had a strong synergistic effect on the LPS-induced secretion of
IL-8,
IL-10, and on monocyte TF activity, but not on
TNFalpha and 1L-6 production. On the other hand, soluble
beta-glucan strongly primed LPS stimulation of all parameters, including
TNFalpha and
IL-6.
beta-Glucan also induced detectable neutrophil degranulation within 15 min, whereas a response to LPS was first detected after 90 min. In conclusion, soluble
beta-1,3-glucan upregulated leukocyte activity, both on its own and in concert with LPS.