Obesity enhances eosinophilic inflammation in a murine model of allergic asthma.
OBJECTIVE
Obesity is associated with deterioration in asthma outcomes. Although airways eosinophil accumulation is characteristic of lung allergic diseases, little is known about the influence of obesity on the allergic eosinophil trafficking from bone marrow to lung tissues, and recruitment to airways lumen. Here, we have assessed the effects of diet-induced obesity on allergic eosinophilic inflammation in mice, examining eosinophil trafficking from bone marrow to airways, and production of T(H)1/T(H)2 cytokines.


METHODS
C57BL/6 mice fed for 10 weeks with standard chow or high-fat diet were sensitized and challenged with ovalbumin. At 24-96 h post-ovalbumin challenge, bronchoalveolar lavage (BAL) fluid, lung tissue and bone marrow were examined.


RESULTS
The high-fat-fed mice exhibited increased body weight and epididymal fat, glucose intolerance and alterations in lipid profile compared with the lean mice. Obesity markedly elevated serum leptin and lowered adiponectin levels. Ovalbumin challenge in obese mice promoted a markedly higher eosinophil accumulation in bone marrow and connective tissue surrounding the bronchial and bronchiolar segments. Eosinophil number in BAL fluid of obese mice was lower at 24 and 48 h. Levels of interleukin (IL)-5, eotaxin, tumour necrosis factor-alpha and IL-10 in BAL fluid of obese mice were significantly higher than in lean mice.


CONCLUSIONS
Diet-induced obesity enhanced eosinophil trafficking from bone marrow to lung tissues, and delayed their transit through the airway epithelium into the airway lumen. Consequently, eosinophils remain longer in lung peribronchiolar segments due to overproduction of T(H)1/T(H)2 cytokines and chemokines.
Calixto
M C
MC
Department of Pharmacology and Internal Medicine, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Lintomen
L
L
Schenka
A
A
Saad
M J
MJ
Zanesco
A
A
Antunes
E
E
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054413:Chemokine CCL11; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D054413:Chemokine CCL11; D016207:Cytokines; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010047:Ovalbumin