Fungal β-glucans modulate macrophage release of tumor necrosis factor-α in response to bacterial lipopolysaccharide

Tumor necrosis factor-alpha (TNFα) is a potent cytokine believed to participate in the development of endotoxin-induced shock and the adult respiratory distress syndrome [1,2]. Treatment of animals with β-glucan prior to bacterial challenge reduces TNFα release and prevents death [3]. We therefore hypothesized that β-glucan might regulate TNFα secretion from macrophages in response to lipopolysaccharide (LPS). Rat alveolar macrophages were cultured in the presence of β-glucan alone and the TNFα secretion quantified using an L929 cytotoxicity assay. Concentrations of β-glucan less than 500 μg/ml were found to stimulate TNFα release from macrophages. However, concentrations of β-glucan greater than 500 μg/ml resulted in suppression of the TNFα activity released. This reduction in TNFα release was not mediated by a toxic effect of β-glucan, as large concentrations of β-glucan had no effect on macrophage viability. We further observed that the incubation of macrophages with large concentrations of β-glucan (500 μg/ml) also inhibited the secretion of TNFα induced by bacterial LPS. Furthermore, interferon-γ (IFNγ), a potent activator of TNFα expression, failed to overcome the inhibition of TNFα caused by β-glucan. These data suggest an immunomodulatory role for β-glucan which may explain both the TNFα-stimulating and -inhibiting effects of fungal β-glucans during infection.