Abstract
Acute respiratory distress syndrome (ARDS) is the most common form of acute severe hypoxemic respiratory failure in the critically ill with a hospital mortality of 40%. Alveolar inflammation is one of the hallmarks for this disease. β-Glucans are polysaccharides isolated from a variety of natural sources including mushrooms, with documented immune modulating properties. To investigate the immunomodulatory activity of β-glucans and their potential as a treatment for ARDS, we isolated and measured glucan-rich polysaccharides from seven species of mushrooms. We used three models of in-vitro injury in THP-1 macrophages, Peripheral blood mononuclear cells (CD14+) (PMBCs) isolated from healthy volunteers and lung epithelial cell lines. We observed variance between β-glucan content in extracts isolated from seven mushroom species. The extracts with the highest β-glucan content found was Lentinus edodes which contained 70% w/w and Hypsizygus tessellatus which contained 80% w/w with low levels of α-glucan. The extracts had the ability to induce secretion of up to 4000 pg/mL of the inflammatory cytokine IL-6, and up to 5000 pg/mL and 500 pg/mL of the anti-inflammatory cytokines IL-22 and IL-10, respectively, at a concentration of 1 mg/mL in THP-1 macrophages. In the presence of cytokine injury, IL-8 was reduced from 15,000 pg/mL to as low as 10,000 pg/mL in THP-1 macrophages. After insult with LPS, phagocytosis dropped from 70-90% to as low 10% in CD14+ PBMCs. After LPS insult CCL8 relative gene expression was reduced, and IL-10 relative gene expression increased from 50 to 250-fold in THP-1 macrophages. In lung epithelial cells, both A549 and BEAS-2B after IL-1β insult, IL-8 levels dropped from 10,000 pg/mL to as low as 6000 pg/mL. TNF-α levels dropped 10-fold from 100 pg/mL to just below 10 pg/mL. These results demonstrate the therapeutic potential of β-glucans in inflammatory lung conditions. Findings also advance bio-based research that connects green innovation with One Health applications for the betterment of society.