Cross-Linking of the β-Glucan Receptor on Human Monocytes Results in Interleukin-1 Receptor Antagonist But Not Interleukin-1 Production

Abstract

AbstractThe β-glucan receptor, found on monocytes and neutrophils, binds glucose polymers derived from fungi. Ligands for the receptor have various immunomodulatory effects, including increased microbicidal killing activity. We have investigated the effect of β-glucans on the production of interleukin-1 (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1 Ra). Particulate β-glucan induced IL-1Ra production from human peripheral blood mononuclear cells (PBMC) but did not stimulate IL-1β synthesis or gene expression in these same cells. Monomeric (soluble) β-glucan did not induce IL-1 Ra production. However, when preincubated with PBMC, monomeric β-glucan significantly [P < .01) reduced particulate β-glucan induction of IL-1 Ra by 40%, suggesting that crosslinking of β-glucan receptors is required for induction of IL-1 Ra. In support of this, monomeric β-glucan immobilized on plastic surfaces stimulated IL-1 Ra production. Vitamin D3, which increases the functional capacity of β-glucan receptors, increased IL-1Ra production induced by particulate β-glucan, whereas dexamethasone suppressed IL-1Ra synthesis. Because of their differential effects on cytokine production, β-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.