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Myoinositol (MI) inhibits Interleukin-6, potential role in COVID-19 disease

- 4 min read
written by Shield Connect

Pathogenic human coronavirus infection that is COVID-19, caused by SARS CoV-2 virus is associated with high mortality of patients in which the virus triggers an interstitial pneumonia that quickly evolves into a severe respiratory distress syndrome.

Pathogenic human coronavirus infection that is COVID-19, caused by SARS CoV-2 virus is associated with high mortality of patients in which the virus triggers an interstitial pneumonia that quickly evolves into a severe respiratory distress syndrome. The disease progresses from mild symptomsto hypoxemia, breathing difficulties and acute respiratory depress syndrome (ARDS) that possibly require hospitalization with ventilation and often leads to death.

COVID-19 disease complications

  • Thrombotic and vascular complications targeting endothelial cells
  • Lymphocytopenia corelates with the severity of the disease
  • Characterized by a suppressed endothelial nitric oxide synthase (eNOS) with nitric oxide (NO) deficiency which is a vasodilator and antithrombotic factor.
  • Patients with cardiometabolic comorbidities (e.g., hypertension, Type-2 Diabetes Mellitus), chronic renal failure, chronic liver failure or immunocompromised patients are considered high risk cases for sever disease)

Interleukin-6 (IL-6) is one of the key factors for the COVID-19 progression and its level is positively correlated with the severity of the disease. The molecular mechanisms for cytokine release syndrome (CRS) in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of CD4 T lymphocytes which are rapidly activated to become pathogenic T helper-1 cells, subsequently unleashing a “cytokine storm” through increased expression of IL-6 and many other cytokines1. These further promotes the recruitment of inflammatory CD14 and CD16 monocytes, activation of immune cells and the secretion of proinflammatory cytokines. Other mechanisms related to release of IL-6 include its interaction with Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon responses. It has been observed that lungs of Sars-CoV-2 patients are infiltrated by many inflammatory cells that disrupt the interstitium and alters the physiological crosstalk between cells and their microenvironment that results in hindering O2 exchange 2which leads to leaking of blood vessels, drop in blood pressure and formation of clots, followed by catastrophic organ failure.

New therapeutic perspectives with Myoinositol inCOVID-19

Myo-inositol (MI) is the most abundant stereoisomer of the inositol family. It is the precursor of Inositol-3-phosphate, a second messenger for several G-protein-coupled receptors (GPCRs).MI significantly targets IL-6 or able to downregulate IL-6 which is effective in blocking inflammatory cytokine storm resulting in reduction of systolic BP, improvement in endothelial function followed by the decrease of radical oxidative species and enhancement of nitric oxidebioactivity.Further it specifically down-regulates the expression phosphatidyl-inositol-3-kinase (PI3K), which is involved in IL-6 signal transduction. Through this mechanism, many inflammatory activities resulting from downstream PI3K activation are inhibited3. Therefore, MI is having a significant treatment potential for severe COVID 19 patients.

Importantly, preliminary research suggested that IL-6drives the inflammatory response that leads to high morbidity and mortality in patients with COVID-19 who develops acuterespiratory distress syndrome. Study further reveals those high concentrations of inositol or its derivatives in surfactant preparations mitigate key pathways in inflammatory lung diseases. Moreover, apart from IL-6, MI downregulates many other inflammatory parameters including PGE and COX2 as well4.Research suggests that a pro-inflammatory cytokineIL-6 is having a major role in chronic inflammation in PCOS too and Enzyme-linked immunosorbent assay (ELISA) revealed that MI significantlyreduced the levels IL-6 in PCOS ratmodel5.

Expression of IL-6 - IMG A IL-6 IMAGE B

Fig 1A:Expression of IL-6 in ovaries of rats analyzed by RT-PCR, 1B.Serum levels of IL-6 by ELISA study5.

Hence, these findings suggest that IL-6 is a major target of myoinositol and raise the possibility that Sars-CoV-2 patients with IL-6-driven inflammation might get benefited from myoinositol treatment.

References

  1. Yifan Que et al., Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality, Int Rev Immunol. 2021 : 1–14.
  2. Jiang S, et al., A novel coronavirus (2019 nCoV) causing pneumonia associated respiratory syndrome. Cell Mol Immunol 2020, doi: 10.1038/s41423-020-0372-4.
  3. Vázquez-Oliva G et al., Lowering of blood pressure leads to decreased circulating interleukin-6 in hypertensive subjects. J Hum Hypertens 2005; 19: 457-462.
  4. Beemster P et al., Involvement of inositol in reproduction. Nutr Rev 2002;60.
  5. Zhang Y et al., Reduced IL-6/ P-STAT 3 associated with myo-inositol, J Med Food 2020, 1–13
Dr Nikhil Varge Dr Nikhil Varge
MBBS MD (Internal Medicine)
Consultant: Acharya Shri Nanesh Hospital in Belapur, Navi Mumbai

 

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