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Substance P antagonist improves both obesity and asthma in a mouse model
Author(s) -
Ramalho R.,
Almeida J.,
Beltrão M.,
Pirraco A.,
Costa R.,
Sokhatska O.,
Guardão L.,
Palmares C.,
Guimarães J. T.,
Delgado L.,
Moreira A.,
Soares R.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12052
Subject(s) - medicine , resistin , endocrinology , ovalbumin , asthma , sensitization , bronchoalveolar lavage , antagonist , immunoglobulin e , inflammation , immunology , leukotriene receptor , obesity , adipokine , lung , receptor , insulin resistance , leukotriene , immune system , antibody
Background Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P ( SP ), involved in neurogenic inflammation by acting through its receptor NK 1‐R, seems to participate in obese–asthma phenotype in mice. Objectives To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet‐induced obesity and asthma. Methods Diet‐induced obese B alb/c mice were sensitized and challenged with ovalbumin ( OVA ) and treated with a selective NK 1‐ R antagonist or placebo. Serum glucose, insulin, IL ‐6, resistin, and OVA ‐specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were measured. Results Ovalbumin‐obese mice treated with NK 1‐ R antagonist had lower weight ( P = 0.0002), reduced daily food intake ( P = 0.0021), reduced daily energy intake ( P = 0.0021), reduced surface adipocyte areas ( P < 0.0001), lower serum glucose ( P = 0.04), lower serum insulin ( P = 0.03), lower serum IL ‐( P = 0.0022), lower serum resistin ( P = 0.0043), lower serum OVA ‐specific IgE ( P = 0.035), and lower peribronchial inflammation score ( P < 0.0001) than nontreated OVA ‐obese mice. We observed an interaction between obesity, allergen sensitization, and treatment with NK 1‐ R antagonist for metabolic and systemic biomarkers, and for allergen sensitization and bronchial inflammation, showing a synergy between these variables. Conclusion & Clinical Relevance In an experimental model of obesity and asthma in mice, NK 1‐R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese–asthma phenotype and highlight SP as a target with potential clinical interest in the obese–asthma epidemics.