Role of inositol to improve surfactant functions and reduce IL-6 levels: A potential adjuvant strategy for SARS-CoV-2 pneumonia?

Abstract

To date, the spread of SARS-CoV-2 infection is increasing worldwide and represents a primary healthcare emergency. Although the infection can be asymptomatic, several cases develop severe pneumonia and acute respiratory distress syndrome (ARDS) characterized by high levels of pro-inflammatory cytokines, primarily interleukin (IL)-6. Based on available data, the severity of ARDS and serum levels of IL-6 are key determinants for the prognosis. In this scenario, available in vitro and in vivo data suggested that myo-inositol is able to increase the synthesis and function of the surfactant phosphatidylinositol, acting on the phosphoinositide 3-kinase (PI3K)-regulated signaling, with amelioration of both immune system and oxygenation at the bronchoalveolar level. In addition, myo-inositol has been found able to decrease the levels of IL-6 in several experimental settings, due to an effect on the inositol-requiring enzyme 1 (IRE1)-X-box-binding protein 1 (XBP1) and on the signal transducer and activator of transcription 3 (STAT3) pathways. In this scenario, treatment with myo-inositol may be able to reduce IL-6 dependent inflammatory response and improve oxygenation in patients with severe ARDS by SARS-CoV-2. In addition, the action of myo-inositol on IRE1 endonuclease activity may also inhibit the replication of SARS-CoV-2, as was reported for the respiratory syncytial virus. Since the available data are extremely limited, if this potential therapeutic approach will be considered valid in the clinical practice, the necessary future investigations should aim to identify the best dose, administration route (oral, intravenous and/or aerosol nebulization), and cluster(s) of patients which may get beneficial effects from this treatment.

Myoinositol Reduces Inflammation and Oxidative Stress in Human Endothelial Cells Exposed In Vivo to Chronic Hyperglycemia

“…Moreover, in a rat model of insulin resistance, a reduction in the pro-inflammatory cytokine IL-6 circulating levels was observed after Myo supplementation [ 39 ]. Interestingly, Myo treatment has been shown to increase synthesis and function of surfactant, improving lung immune defense response [ 40 ].…”

Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function

“…Besides pulmonary uncontrolled inflammation, oxidative stress during the injury process, which supply an excess amount of molecular oxygen to the tissues [ 43 , 44 ], also play an important role in ALI [ 26 ]. However, over the past decades, although great achievement has been made in the field of understanding the pathogenesis of ARDS/ALI, such as inositol could improve the surfactant functions and reduce IL-6 levels [ 45 ] or targeting IL-6 and other cytokine-induced “cytokine storm” [ 46 ] to alleviate ARDS, little convincing therapeutic strategies or agents are available to fully control the excessive inflammation until now. Thus, finding novel treatment approaches to govern the superfluous inflammation seems to be critical.…”

A Targeted Serum Metabolomics GC-MS Approach Identifies Predictive Blood Biomarkers for Retained Placenta in Holstein Dairy Cows

“…Intriguingly, MI has been reported as an anti-inflammatory agent, suppressing the production of proinflammatory cytokines and enhancing phagocytic capabilities of macrophages against antibiotic-resistant E. coli [ 56 , 57 ]. A recent review by Laganà et al [ 58 ] summarized research indicating MI was able to lower the concentration of IL-6 in a whole variety of inflammatory conditions. Interleukin-6 is a multifunctional cytokine that regulates both humoral and cellular responses, playing an important function in inflammation and tissue damage during infections [ 59 ].…”