Lidocaine reduces neutrophil recruitment by abolishing chemokine-induced arrest and transendothelial migration in septic patients
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Output type: Journal article
Author list: Berger C., Rossaint J., Van Aken H., Westphal M., Hahnenkamp K., Zarbock A.
Publisher: American Association of Immunologists
Publication year: 2014
Journal: The Journal of Immunology (0022-1767)
Volume number: 192
Issue number: 1
Start page: 367
End page: 376
Number of pages: 10
ISSN: 0022-1767
eISSN: 1550-6606
URL: http://api.elsevier.com/content/abstract/scopus_id:84891069094
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Open access status: bronze
Full text URL: https://www.jimmunol.org/content/jimmunol/192/1/367.full.pdf
Abstract
The inappropriate activation, positioning, and recruitment of leukocytes are implicated in the pathogenesis of multiple organ failure in sepsis. Although the local anesthetic lidocaine modulates inflammatory processes, the effects of lidocaine in sepsis are still unknown. This double-blinded, prospective, randomized clinical trial was conducted to investigate the effect of lidocaine on leukocyte recruitment in septic patients. Fourteen septic patients were randomized to receive either a placebo (n = 7) or a lidocaine (n = 7) bolus (1.5 mg/kg), followed by continuous infusion (100 mg/h for patients >70 kg or 70 mg/h for patients <70 kg) over a period of 48 h. Selectin-mediated slow rolling, chemokine-induced arrest, and transmigration were investigated by using flow chamber and transmigration assays. Lidocaine treatment abrogated chemokine-induced neutrophil arrest and significantly impaired neutrophil transmigration through endothelial cells by inhibition of the protein kinase C-θ while not affecting the selectin-mediated slow leukocyte rolling. The observed results were not attributable to changes in surface expression of adhesion molecules or selectinmediated capturing capacity, indicating a direct effect of lidocaine on signal transduction in neutrophils. These data suggest that lidocaine selectively inhibits chemokine-induced arrest and transmigration of neutrophils by inhibition of protein kinase C-θ while not affecting selectin-mediated slow rolling. These findings may implicate a possible therapeutic role for lidocaine in decreasing the inappropriate activation, positioning, and recruitment of leukocytes during sepsis. Copyright © 2013 by The American Association of Immunologists, Inc.
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