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From nicotine to the cholinergic anti-inflammatory reflex - Can nicotine alleviate the dysregulated inflammation in COVID-19?
Gauthier, Alex G; Lin, Mosi; Wu, Jiaqi; Kennedy, Thomas P; Daley, Lee-Anne; Ashby, Charles R; Mantell, Lin L.
  • Gauthier AG; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
  • Lin M; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
  • Wu J; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
  • Kennedy TP; School of Medicine, Tulane University, New Orleans, LA, USA.
  • Daley LA; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
  • Ashby CR; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
  • Mantell LL; Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522
Semantic information from SemMedBD (by NLM)
1. nicotine TREATS Inflammation
Subject
nicotine
Predicate
TREATS
Object
Inflammation
2. nicotine ASSOCIATED_WITH COVID-19
Subject
nicotine
Predicate
ASSOCIATED_WITH
Object
COVID-19
3. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
4. Respiratory Distress Syndrom OCCURS_IN C0030705
Subject
Respiratory Distress Syndrom
Predicate
OCCURS_IN
Object
C0030705
5. Respiratory Failure OCCURS_IN Patients
Subject
Respiratory Failure
Predicate
OCCURS_IN
Object
Patients
6. Therapeutic procedure TREATS Inflammation
Subject
Therapeutic procedure
Predicate
TREATS
Object
Inflammation
7. Inflammation OCCURS_IN Patients
Subject
Inflammation
Predicate
OCCURS_IN
Object
Patients
8. Airway structure LOCATION_OF HMGB1 Protein
Subject
Airway structure
Predicate
LOCATION_OF
Object
HMGB1 Protein
9. GTS-21 TREATS Respiratory Distress Syndrom
Subject
GTS-21
Predicate
TREATS
Object
Respiratory Distress Syndrom
10. High Level PROCESS_OF Patients
Subject
High Level
Predicate
PROCESS_OF
Object
Patients
11. nicotine AFFECTS Transcriptional Activation
Subject
nicotine
Predicate
AFFECTS
Object
Transcriptional Activation
12. nicotine TREATS Inflammatory Response
Subject
nicotine
Predicate
TREATS
Object
Inflammatory Response
13. GTS-21 TREATS Inflammatory Response
Subject
GTS-21
Predicate
TREATS
Object
Inflammatory Response
14. Inflammatory Response PROCESS_OF Patients
Subject
Inflammatory Response
Predicate
PROCESS_OF
Object
Patients
15. nicotine TREATS Inflammation
Subject
nicotine
Predicate
TREATS
Object
Inflammation
16. nicotine ASSOCIATED_WITH COVID-19
Subject
nicotine
Predicate
ASSOCIATED_WITH
Object
COVID-19
17. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
18. Respiratory Distress Syndrome, Adult OCCURS_IN Patients
Subject
Respiratory Distress Syndrome, Adult
Predicate
OCCURS_IN
Object
Patients
19. Respiratory Failure OCCURS_IN Patients
Subject
Respiratory Failure
Predicate
OCCURS_IN
Object
Patients
20. Therapeutic procedure TREATS Inflammation
Subject
Therapeutic procedure
Predicate
TREATS
Object
Inflammation
21. Inflammation OCCURS_IN Patients
Subject
Inflammation
Predicate
OCCURS_IN
Object
Patients
22. Airway structure LOCATION_OF HMGB1 Protein
Subject
Airway structure
Predicate
LOCATION_OF
Object
HMGB1 Protein
23. GTS-21 TREATS Respiratory Distress Syndrome, Adult
Subject
GTS-21
Predicate
TREATS
Object
Respiratory Distress Syndrome, Adult
24. High Level PROCESS_OF Patients
Subject
High Level
Predicate
PROCESS_OF
Object
Patients
25. nicotine AFFECTS Transcriptional Activation
Subject
nicotine
Predicate
AFFECTS
Object
Transcriptional Activation
26. nicotine TREATS Inflammatory Response
Subject
nicotine
Predicate
TREATS
Object
Inflammatory Response
27. GTS-21 TREATS Inflammatory Response
Subject
GTS-21
Predicate
TREATS
Object
Inflammatory Response
28. Inflammatory Response PROCESS_OF Patients
Subject
Inflammatory Response
Predicate
PROCESS_OF
Object
Patients
ABSTRACT
The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyridines / Tobacco Use Disorder / Benzylidene Compounds / Cholinergic Agents / SARS-CoV-2 / COVID-19 / Inflammation / Nicotine Limits: Humans Language: English Journal: J Immunotoxicol Journal subject: Allergy and Immunology / Toxicology Year: 2021 Document Type: Article Affiliation country: 1547691x.2021.1875085

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyridines / Tobacco Use Disorder / Benzylidene Compounds / Cholinergic Agents / SARS-CoV-2 / COVID-19 / Inflammation / Nicotine Limits: Humans Language: English Journal: J Immunotoxicol Journal subject: Allergy and Immunology / Toxicology Year: 2021 Document Type: Article Affiliation country: 1547691x.2021.1875085