BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Sébastien Talbot; Raja-Elie E Abdulnour; Patrick R Burkett; Seungkyu Lee; Shane J F Cronin; Maud A Pascal; Cedric Laedermann; Simmie L Foster; Johnathan V Tran; Nicole Lai; Isaac M Chiu; Nader Ghasemlou; Matthew DiBiase; David Roberson; Christian Von Hehn; Busranour Agac; Oliver Haworth; Hiroyuki Seki; Josef M Penninger; Vijay K Kuchroo; Bruce P Bean; Bruce D Levy; Clifford J Woolf Journal: Neuron Date: 2015-06-25 Impact factor: 17.173
Authors: A C Reis; A L Alessandri; R M Athayde; D A Perez; J P Vago; T V Ávila; T P T Ferreira; A C S de Arantes; D de Sá Coutinho; M A Rachid; L P Sousa; M A Martins; G B Menezes; A G Rossi; M M Teixeira; V Pinho Journal: Cell Death Dis Date: 2015-02-12 Impact factor: 8.469
Authors: Diego S Coutinho; Edna A Anjos-Valotta; Caio V M F do Nascimento; Ana Lucia A Pires; Marcelo H Napimoga; Vinícius F Carvalho; Rafael C Torres; Patrícia M R E Silva; Marco A Martins Journal: Front Immunol Date: 2017-06-30 Impact factor: 7.561
Authors: Isabelle Karine da Costa Nunes; Everton Tenório de Souza; Suzana Vanessa S Cardozo; Vinicius de Frias Carvalho; Nelilma Correia Romeiro; Patrícia Machado Rodrigues E Silva; Marco Aurélio Martins; Eliezer J Barreiro; Lídia Moreira Lima Journal: PLoS One Date: 2016-10-03 Impact factor: 3.240