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

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Previous research has shown that rapid replication of the virus, Coronavirus pneumonia, can cause uncontrolled immune responses that lead to acute lung injury, respiratory distress, and death. This study, published by Murphy et al. in 2020, used cell lines to focus on the ability of different extracts of mushroom-derived (Lentinus edodes/Lentinan) beta glucan to reduce immune reactions and respiratory stress similar to those caused by Coronavirus pneumonia.

The goal of the study was to understand if different extracts of beta glucan from Lentinan had any effect on reducing inflammation and stress in cellular models of lung injury and macrophage (type of immune cell) activity similar to the effects of Coronavirus pneumonia viral infection. Researchers analyzed the Lentinan extracts for composition and immunomodulatory activity. Both immune (macrophages) and lung cells were utilized in these experiments using various methods to determine if extracts of Lentinan reversed the effects of injury, heightened immune response, and stress. The researchers observed varying immunomodulatory activities when comparing different Lentinan extracts, demonstrating significant differences between these extracts. Overall, the findings supported immunomodulatory and pulmonary protective effects.

While the experiments were well designed and the results are informative, the researchers did not actually test the efficacy of these Lentinan extracts using cell models infected by the COVID-19 virus. Instead, they chose to model similar effects that have been observed due to COVID-19 infection. Thus, the claim that this treatment has implications for applicability to the Coronavirus is premature. Cellular and animal studies should be conducted using Lentinan extracts against Coronavirus infection to definitively determine possible therapeutic efficacy.

Abstract

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.

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