"Cytokine Storm" (Inflammation Response)

At the time of this writing (Sept. 12, 2020), worldwide COVID-19 cases have been reported to be over 29+ million with 929+ thousand deaths.  These are incredibly high numbers compared to the more common influenza virus.

Many believe that "cytokine storm" is one of the main causes of fatal outcomes from the disease. The cytokine storm is a significant increase in inflammatory molecules in the course of the body's immune response upon encountering a virus.

Theories have been developed that managing this organism's overreaction is one of the key stages in dealing with a worldwide pandemic. Statistics so far show that the main cause of death is acute respiratory syndrome (ARDS). Second is the cytokine storm syndrome (CSS) in various forms, which is accompanied by systemic damage to different organs. In adult patients, CSS has been found to cause 3.7-4.3% of cases of systemic sepsis. In 50% of cases, CSS results in the development of acute respiratory syndrome and other pulmonary and respiratory disorders (Puja Mehta et al., 2020). 

As with previous pandemics (SARS, MARS), routine use of corticosteroids as a therapy is not recommended and may exacerbate lung damage caused by COVID-19. At this stage, immunosuppression sounds like the most promising approach to controlling and reducing the effects of CSS.

This can be achieved by inducing increased production of anti-inflammatory molecules, such as IL-10, that regulate the expression of the immune response in the body (Sarah E Ward et al, 2005). The effect of the anti-inflammatory cytokine interleukin 10 (IL-10) on conditions of acute respiratory syndrome induced by pathogenic lipopolysaccharides in animal models was observed.

Mortality was found to decrease by 30% when experimentally established concentrations of IL-10 were administered. There is a significant decrease in changes in lung tissue due to inflammatory processes. Expression of the inflammatory cytokine TNF-α, which has been found to be directly related to lung damage at elevated concentrations due to viral infections, is decreased. In addition, IL-10 attachment inhibits the overactivity of non-specialized immune response cells, such as neutrophils and macrophages.

All these results lead to the conclusion that IL-10 is clearly associated with reducing lung damage due to unlocked inflammatory processes in the body and its potential for clinical use (Gen Inoue, 2000). 

The results obtained in animal models have also been confirmed in clinical studies with patients with pandemic viral infections with high statistical morbidity and mortality, such as SARS-CoV. IL-10 does not affect the clearance of the virus in the body, but affects the cells of innate and adaptive immunity. Its main advantage is that it reduces inflammatory processes and fibrosis of tissues and organs, as a subsequent effect of the viral infection (Kayla A. Weiss et al., 2011). 

The analysis of the immunological status of patients at different stages of development of SARS-CoV infection shows a significant increase in the levels of IL-10 in patients treated for the infection. This is a prerequisite for further in-depth studies on the protective properties of IL-10 for detecting the possibility of preventing the development of viral diseases by administering increased concentrations of the anti-inflammatory cytokine (Yuanchun Zhang et al., 2004). 

At the same time, a very good positive effect of Lung Immunity Support Probiotic has been demonstrated, namely the ability to greatly enhance the production of an important anti-inflammatory interleukin such as IL-10. From the test results of the product, it is shown that it is able to induce the synthesis of much higher amounts of IL-10 by splenocytes than the splenocyte control sample.*

All these in vitro immunological results demonstrate the strong anti-inflammatory potential of the Lung Immunity Support Probiotic. This, together with the results of clinical studies of the complex of polypeptides and lipopolysaccharides, having been proven by Acad. Bogdan Petrunov and his team, suggests that the product can "support" our immune system to deal with secondary bacterial pneumonia (Maria Nikolova et al., 2009). It also evidences the ability of Lung Immunity Support Probiotic to influence our immune system positively by acting as an anti-inflammatory upon initial encounter with a pathogenic microorganism (pathogenic bacteria, viruses and fungal agents). An additional positive effect would be its leading to the formation of a specific immune response to the underlying bacteria leading to the development of pneumonia.*

*All statements herein have not been evaluated by the Food and Drug Administration. The products on this website were not intended to diagnose, treat, cure, or prevent any disease.

References: 

1. Gen Inoue (2000), Effect of interleukin-10 (IL-10) on experimental LPS-induced acute lung injury, Journal of Infection and Chemotherapy, Volume 6, Issue 1, 2000, Pages 51-60. https://www.sciencedirect.com/science/article/abs/pii/S1341321X00713377
   
   
2. Jennifer R. Tisoncik, Marcus J. Korth, Cameron P. Simmons, Jeremy Farrar, Thomas R. Martin, and Michael G. Katze (2012), Into the Eye of the Cytokine Storm, Microbiol Mol Biol Rev. 2012 Mar; 76(1): 16–32; doi: 10.1128/MMBR.05015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/
   
   
3. Kayla A. Weiss, Allison F. Christiaansen, Ross B. Fulton, David K. Meyerholz and Steven M. Varga (2011), Multiple CD4+ T Cell Subsets Produce Immunomodulatory IL-10 During Respiratory Syncytial Virus Infection, Journal of Immunology, September 15, 2011, 187 (6) 3145-3154; DOI: https://doi.org/10.4049/jimmunol.1100764. https://www.jimmunol.org/content/187/6/3145
   
   
4. Maria Nikolova, Draganka Stankulova, Hristo Taskova, Plamen Nenkov, Vladimir Maximov, Bogdan Petrunov (2009), Polybacterial immunomodulator Respivax restores the inductive function of innate immunity in patients with recurrent respiratory infections. https://www.sciencedirect.com/science/article/pii/S1567576909000216?via%3Dihub
   
   
5. Puja Mehta, Daniel F McAuley, Michael Brown, Emilie Sanchez, Rachel S Tattersall, Jessica J Manson (2020), COVID-19: consider cytokine storm syndromes and immunosuppression, CORRESPONDENCE, Volume 395, Issue 10229, p. 1033-1034, March 28, 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext
   
   
6. Sarah E Ward, Mona R Loutfy, Lawrence M Blatt, Katharine A Siminovitch, Jiabing Chen, Anna Hinek, Bryan Wolff, Dieu H Pham, Hassan Deif, Elizabeth A LaMere, Kevin C Kain, Gabriella A Farcas, Patti Ferguson, Mary Latchford, Gary Levy, Liasum Fung, James W Dennis, Enoch KY Lai and Eleanor N Fish (2005), Dynamic changes in clinical features and cytokine/chemokine responses in SARS patients treated with interferon alfacon-1 plus corticosteroids, Antiviral Therapy, 2005;10(2):263-75. https://www.ncbi.nlm.nih.gov/pubmed/15865221
   
   
7. Yuanchun Zhang, Jing Li, Yuliang Zhan, Lianqiu Wu, Xueying Yu, Wenjian Zhang, Liya Ye, Shiqing Xu, Ruihua Sun,Yunting Wang, and Jinning Lou (2004), Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome, Infection and Immunity, 2004 Aug; 72(8): 4410–4415; doi: 10.1128/IAI.72.8.4410- 4415.2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC470699/ 16.04.2020