Substance P antagonist improves both obesity and asthma in a mouse model

• Published in: Allergy (Copenhagen) Vol. 68; no. 1; pp. 48 - 54
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.01.2013
• Subjects: Adipocytes; Allergens; Allergens - immunology; Alveoli; animal model; Animal models; Animals; Asthma; Asthma - drug therapy; Asthma - metabolism; biomarkers; Biomarkers - metabolism; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - immunology; Bronchitis - drug therapy; Bronchitis - immunology; Bronchus; Causality; Disease Models, Animal; Energy intake; Epidemics; Food intake; Genotype & phenotype; Glucose; Immunoglobulin E; Inflammation; Insulin; Interleukin 6; Lung; Mice; Neurokinin-1 Receptor Antagonists; NK1‐R antagonist; Obesity; Obesity - drug therapy; Obesity - metabolism; Ovalbumin; Substance P; Substance P - metabolism; Substance P receptors; treatment
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12052

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 NK1‐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 Balb/c mice were sensitized and challenged with ovalbumin (OVA) and treated with a selective NK1‐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 NK1‐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 NK1‐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, NK1‐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.