epiglucan and Pneumonia--Viral

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.

Topics: beta-Glucans; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Immunotherapy; Pandemics; Pneumonia, Viral; SARS-CoV-2; Shiitake Mushrooms

As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. Throughout the literature, it has been shown that the induction of TRIM using such inducers as the BCG vaccine and β-glucan can provide protection through altered immune responses against a range of viral infections. Here we hypothesize a potential role for β-glucan in decreasing worldwide morbidity and mortality due to COVID-19, and posit several ideas as to how TRIM may actually shape the observed epidemiological phenomena related to COVID-19. We also evaluate the potential effects of β-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral β-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of β-glucan's from various sources.

Topics: Administration, Oral; Adult; Age Factors; Animals; Antiviral Agents; BCG Vaccine; beta-Glucans; Betacoronavirus; Child; Coronavirus Infections; COVID-19; Cytokines; Dietary Fiber; Epigenesis, Genetic; Humans; Immunity, Innate; Immunologic Memory; Pandemics; Pneumonia, Viral; Pre-Exposure Prophylaxis; SARS-CoV-2

Topics: Adult; B-Lymphocytes; beta-Glucans; Betacoronavirus; Case-Control Studies; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Coronavirus Infections; COVID-19; Disease Progression; Female; Humans; Interleukin-10; Interleukin-6; Killer Cells, Natural; Lung; Lymphocyte Count; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; Proteoglycans; SARS-CoV-2; Severity of Illness Index; Survival Analysis; Tomography, X-Ray Computed