Neurogenic inflammation in allergen-challenged obese mice: A missing link in the obesity-asthma association?
OBJECTIVE
A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice.


METHODS
High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi.


RESULTS
Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R(2) = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001).


CONCLUSIONS
Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.
Department of Immunology, Faculty of Medicine, University of Porto, Porto, Portugal. rrenata@med.up.pt
Renata
R
Ramalho
Joana
J
Almeida
Marília
M
Beltrão
Ana
A
Pirraco
Raquel
R
Costa
Oksana
O
Sokhatska
Luísa
L
Guardão
Carmo
C
Palmares
João Tiago
JT
Guimarães
Luís
L
Delgado
André
A
Moreira
Raquel
R
Soares
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001786:Blood Glucose / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002452:Cell Count; D059305:Diet, High-Fat; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007328:Insulin / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008820:Mice, Obese; D020078:Neurogenic Inflammation / Q000276:immunology* / Q000473:pathology*; D009765:Obesity / Q000276:immunology* / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D013373:Substance P / Q000097:blood / Q000276:immunology; D015320:Tachykinins / Q000097:blood / Q000276:immunology
D000485:Allergens; D001786:Blood Glucose; D007328:Insulin; D015320:Tachykinins; D013373:Substance P; D007073:Immunoglobulin E; D010047:Ovalbumin