β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects — Implications for coronavirus disease (COVID-19) immunotherapies

• Published in: The Science of the total environment Vol. 732; p. 139330
• Main Authors: Murphy, Emma J., Masterson, Claire, Rezoagli, Emanuele, O'Toole, Daniel, Major, Ian, Stack, Gary D., Lynch, Mark, Laffey, John G., Rowan, Neil J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.08.2020; The Authors. Published by Elsevier B.V
• Subjects: beta-Glucans; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine storm; Disease mitigation; Humans; Immunomodulation; Immunotherapy; Medicinal mushroom; Pandemics; Pneumonia, Viral; SARS-CoV-2; Shiitake Mushrooms; β-Glucans; COVID-19; Disease mitigation; β-Glucans; Immunomodulation; Cytokine storm; Medicinal mushroom
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2020.139330

Coronavirus pneumonia is accompanied by rapid virus replication, where a large number of inflammatory cell infiltration and cytokine storm may lead to acute lung injury, acute respiratory distress syndrome (ARDS) and death. The uncontrolled release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, is associated with ARDS. This constituted the first study to report on the variability in physicochemical properties of β-glucans extracts from the same edible mushroom Lentinus edodes on the reduction of these pro-inflammatory cytokines and oxidative stress. Specifically, the impact on the immunomodulatory and cytoprotective properties of our novel in ‘house’ (IH-Lentinan, IHL) and a commercial (Carbosynth-Lentinan, CL) Lentinan extract were investigated using in vitro models of lung injury and macrophage phagocytosis. CL comprised higher amounts of α-glucans and correspondingly less β-glucans. The two lentinan extracts demonstrated varying immunomodulatory activities. Both Lentinan extracts reduced cytokine-induced NF-κB activation in human alveolar epithelial A549 cells, with the IHL extract proving more effective at lower doses. In contrast, in activated THP-1 derived macrophages, the CL extract more effectively attenuated pro-inflammatory cytokine production (TNF-α, IL-8, IL-2, IL-6, IL-22) as well as TGF-β and IL-10. The CL extract attenuated oxidative stress-induced early apoptosis, while the IHL extract attenuated late apoptosis. Our findings demonstrate significant physicochemical differences between Lentinan extracts, which produce differential in vitro immunomodulatory and pulmonary cytoprotective effects that may also have positive relevance to candidate COVID-19 therapeutics targeting cytokine storm. [Display omitted] •β-Glucans from shiitake mushroom reduces IL-1β, IL-6 in in vitro lung injury model.•β-Glucans from same source can differ in immunomodulatory and pulmonary cytoprotective effects.•β-Glucans can reduce oxidative stress and activate macrophages.•β-Glucans may ameliorate cytokine storm that causes ARDS as seen with COVID-19.