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Lidocaine Reinforces the Anti-inflammatory Action of Dexamethasone on Myeloid and Epithelial Cells Activated by Inflammatory Cytokines or SARS-CoV-2 Infection

Overview
Journal Biomed J
Publisher Elsevier
Specialty General Medicine
Date 2022 Aug 10
PMID 35948250
Authors
Affiliations
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Abstract

Background: Severe cases of Coronavirus Disease 2019 (COVID-19) that require admission to the Intensive Care Unit (ICU) and mechanical ventilation assistance show a high mortality rate with currently few therapeutic options available. Severe COVID-19 is characterized by a systemic inflammatory condition, also called "cytokine storm", which can lead to various multi-organ complications and ultimately death. Lidocaine, a safe local anesthetic that given intravenously is used to treat arrhythmias, has long been reported to have an anti-inflammatory and pro-homeostatic activity.

Methods: We studied the capacity of lidocaine to modulate cytokine secretion of mouse and human myeloid cell lines activated by different cytokines or Toll Like Receptor (TLR) ligands (flagellin (FliC), Lipopolysaccharide (LPS), Polyinosinic:polycytidylic acid (Poly I:C) and N-Palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine x 3HCl (Pam3Cys-SKKKK)) or by Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection to epithelial cells. Reporter cell lines were used to study modulation of lidocaine of specific signaling pathways.

Results: Lidocaine used in combination with dexamethasone, had an additive effect in the modulation of cellular inflammatory response triggered by Tumoral Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1β) as well as different TLR ligands. We also found that lidocaine in combination with dexamethasone modulates the Nuclear factor kappa B (NF-κB) pathway, inflammasome activation as well as interferon gamma receptor (IFNγR) signaling without affecting the type I interferons (Type I IFNs) pathway. Furthermore, we showed that lidocaine and dexamethasone treatment of epithelial cells infected with SARS-CoV-2 modulated the expression of chemokines that contribute to pro-inflammatory effects in severe COVID.

Conclusions: We reported for the first time in vitro anti-inflammatory capacity of lidocaine on SARS-CoV-2 triggered immune pathways. These results indicated the potential of lidocaine to treat COVID-19 patients and add tools to the therapeutic options available for these concerning cases.

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References
1.
Horby P, Lim W, Emberson J, Mafham M, Bell J, Linsell L . Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 384(8):693-704. PMC: 7383595. DOI: 10.1056/NEJMoa2021436. View

2.
Fernandez A, Sanchez-Tarjuelo R, Cravedi P, Ochando J, Lopez-Hoyos M . Review: Ischemia Reperfusion Injury-A Translational Perspective in Organ Transplantation. Int J Mol Sci. 2020; 21(22). PMC: 7696417. DOI: 10.3390/ijms21228549. View

3.
Tang N, Li D, Wang X, Sun Z . Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18(4):844-847. PMC: 7166509. DOI: 10.1111/jth.14768. View

4.
Morris G, Bortolasci C, Puri B, Marx W, ONeil A, Athan E . The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?. Cytokine. 2021; 144:155593. PMC: 8149193. DOI: 10.1016/j.cyto.2021.155593. View

5.
Muller M, Lefebvre F, Harlay M, Glady L, Becker G, Muller C . Impact of intravenous lidocaine on clinical outcomes of patients with ARDS during COVID-19 pandemia (LidoCovid): A structured summary of a study protocol for a randomised controlled trial. Trials. 2021; 22(1):131. PMC: 7876973. DOI: 10.1186/s13063-021-05095-x. View