scholarly journals Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression

2020 ◽  
Vol 21 (17) ◽  
pp. 6244
Author(s):  
Amira Mohammed ◽  
Hasan F.K. Alghetaa ◽  
Kathryn Miranda ◽  
Kiesha Wilson ◽  
Narendra P. Singh ◽  
...  

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ji Hoon Jang ◽  
Hang Jea Jang ◽  
Hyun-Kuk Kim ◽  
Jin Han Park ◽  
Hyo-Jung Kim ◽  
...  

Abstract Background Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important. Case presentation This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department. Conclusions To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Braira Wahid ◽  
Noshaba Rani ◽  
Muhammad Idrees

Abstract After wreaking havoc on a global level with a total of 5,488,825 confirmed cases and 349,095 deaths as of May 2020, severe acute respiratory syndrome coronavirus 2 is truly living up to the expectations of a 21st-century pandemic. Since the major cause of mortality is a respiratory failure from acute respiratory distress syndrome, the only present-day management option is supportive as the transmission relies solely on human-to-human contact. Patients suffering from coronavirus disease 2019 (COVID-19) should be tested for hyper inflammation to screen those for whom immunosuppression can increases chances of survival. As more and more clinical data surfaces, it suggests patients with mild or severe cytokine storms are at greater risk of failing fatally and hence these cytokine storms should be targets for treatment in salvaging COVID-19 patients.


2020 ◽  
Vol 5 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Hesam Khodadadi ◽  
Évila Lopes Salles ◽  
Abbas Jarrahi ◽  
Fairouz Chibane ◽  
Vincenzo Costigliola ◽  
...  

Immunotherapy ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1127-1132 ◽  
Author(s):  
Juan David Cala-García ◽  
Juan David Sierra-Bretón ◽  
Jorge Eduardo Cavelier-Baiz ◽  
Álvaro A Faccini-Martínez ◽  
Carlos Eduardo Pérez-Díaz

Background: Severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 is a challenge for nowadays medical practice. Although there is no clarity in the principal mechanism of lung damage and ARDS development, it has been suggested that one of the main reasons of this pathology is the hyperactivation of the immune system, better known as cytokine storm syndrome. Tocilizumab has been proposed to treat COVID-19 severe cases associated to ARDS. Results & methodology: Here we present two successful cases of tocilizumab administration in two COVID-19 patients with prior administration of antiviral therapy (hydroxychloroquine, azithromycin, lopinavir and ritonavir) with adequate response and resolution of ARDS, septic shock and severe pneumonia within the first 72 h. Discussion & conclusion: This case supports the usage of tocilizumab as an effective therapy in COVID-19 associated cytokine storm syndrome. Further studies should be done in order to assess its effectiveness and security.


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