Nebulized Lidocaine Prevents Airway Inflammation, Peribronchial Fibrosis, and Mucus Production in a Murine Model of Asthma

Evidence suggests that nebulized lidocaine is beneficial in asthma therapy, but to what extent and the mechanisms underlying this effect remain poorly understood. The aim of this study was to assess the impact of lidocaine treatment using a murine model of allergic asthma characterized by expression...

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Published in:	Anesthesiology (Philadelphia) Vol. 117; no. 3; pp. 580 - 591
Main Authors:	SERRA, Magda F, ANJOS-VALOTTA, Edna A, CORDEIRO, Renato S. B, SILVA, Patricia M. R, MARTINS, Marco A, OLSEN, Priscilla C, COUTO, Gina C, JURGILAS, Patricia B, COTIAS, Amanda C, PAO, Camila R, FERREIRA, Tatiana P. T, ARANTES, Ana C. S, PIRES, Ana L. A
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 01-09-2012
Subjects:	Anesthesia Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anesthetics, Local - pharmacology Animals Asthma - drug therapy Asthma - immunology Asthma - pathology Biological and medical sciences Bronchi - pathology Disease Models, Animal Fibrosis GATA3 Transcription Factor - analysis GATA3 Transcription Factor - antagonists & inhibitors Lidocaine - administration & dosage Lidocaine - pharmacology Lung - pathology Male Matrix Metalloproteinase 9 - metabolism Medical sciences Mice Mucus - secretion Nebulizers and Vaporizers T-Lymphocytes - drug effects Lung disease Respiratory disease Rodentia Anticonvulsant Inflammation Mucus Antiarrhythmic agent Asthma Local anesthetic Vertebrata Mammalia Mouse Animal Fibrosis Bronchus disease Anesthesia Organic amide Obstructive pulmonary disease Lidocaine
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Summary:	Evidence suggests that nebulized lidocaine is beneficial in asthma therapy, but to what extent and the mechanisms underlying this effect remain poorly understood. The aim of this study was to assess the impact of lidocaine treatment using a murine model of allergic asthma characterized by expression of pivotal features of the disease: inflammation, mucus production, and lung remodeling. A/J mice sensitized with ovalbumin were treated with inhaled lidocaine or vehicle immediately after ovalbumin intranasal challenges. Lung function, total and differential leukocytes in bronchoalveolar lavage fluid, peribronchial eosinophil density, interleukin (IL)-4, IL-5 and eotaxin-1 levels, epithelial mucus, collagen, extracellular-matrix deposition, matrix metalloproteinase-9 activity, and GATA-3 expression were evaluated. Between five and eight animals per group were used. Inhaled lidocaine inhibited ovalbumin-induced airway hyperreactivity to methacholine, and accumulation of lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid 24 h after the last allergen provocation. Lidocaine administration also prevented other pathophysiological changes triggered by ovalbumin in lung tissue, including peribronchial eosinophil and neutrophil infiltration, subepithelial fibrosis, increased content of collagen and mucus, matrix metalloproteinase-9 activity, and increased levels of IL-4, IL-5, IL-13, and eotaxin-1. Furthermore, inhaled lidocaine inhibited lung tissue GATA-3 expression in ovalbumin-challenged mice. We also demonstrated that lidocaine inhibited the expression of GATA-3 in ovalbumin-stimulated T cells in vitro. Inhaled lidocaine prevents eosinophilic inflammation, overproduction of mucus, and peribronchial fibrosis in a murine model of asthma, and impaired airway hyperreactivity, possibly by inhibiting allergen-evoked GATA-3 expression and the subsequent up-regulation of proinflammatory cytokines and chemokines.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0003-3022 1528-1175
DOI:	10.1097/ALN.0b013e31826687d5