NDLI: Lidocaine reduces neutrophil recruitment by abolishing chemokine-induced arrest and transendothelial migration in septic patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Van Aken, Hugo Zarbock, Alexander Berger, Christian Rossaint, Jan Westphal, Martin Hahnenkamp, Klaus
Description	Country affiliation: Germany Author Affiliation: Berger C ( Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, 48149 Münster, Germany.)
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-Î¸ while not affecting the selectin-mediated slow leukocyte rolling. The observed results were not attributable to changes in surface expression of adhesion molecules or selectin-mediated 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-Î¸ 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Lidocaine Pharmacology Neutrophil Infiltration Drug Effects Immunology Neutrophils Sepsis Transendothelial And Transepithelial Migration Anesthetics, Local Cell Adhesion Molecules Metabolism Cell Cycle Checkpoints Cell Membrane Chemokines Administration & Dosage Phosphorylation Protein Kinase C Selectins Diagnosis Microbiology Clinical Trial Randomized Controlled Trial Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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