title: High-fat feeding redirects cytokine responses and decreases allergic airway eosinophilia.
abstract: BACKGROUND
  Dietary fat intake has been associated with obesity and obesity in its turn with attenuated airway function and asthma, but it is unclear whether or how high-fat intake per se alters immune function relevant to development of allergic asthma.
  
  
  OBJECTIVE
  To use a non-obese mouse model of mild to moderate allergic asthma to compare effects of high-fat with isocaloric control-diet on allergic immune responses.
  
  
  METHODS
  C57BL/6 mice weaned and maintained on control (11% fat calories) or isocaloric high-fat diet (58% fat calories) were systemically sensitized with ovalbumin and challenged in the lungs. Allergic airway inflammation was assessed by measuring lung inflammation; serum antibodies; and, cytokines in serum, bronchoalveolar lavage (BAL) fluid and in supernatants of in vitro stimulated lung draining lymph node and spleen lymphocytes.
  
  
  RESULTS
  There was a significant reduction in lung eosinophilia and IL-5 in high-fat fed mice. Lung draining lymph node cells from these mice showed reduced pro-inflammatory cytokine (MCP-1 and TNF-alpha) release after ovalbumin re-stimulation and reduced release of IL-13 after concanavalin-A stimulation, indicating a general rather than just an antigen-specific change. There was no difference in IFN-gamma release. In contrast, pro-inflammatory cytokine release was increased from splenocytes. Decreased eosinophilia was not due to increased regulatory T cell or IL-10 induction in draining lymph nodes or spleen, nor to changes in antibody response to ovalbumin. However, decreased levels of serum and BAL eotaxin were found in high-fat fed animals.
  
  
  CONCLUSIONS
  The data indicate that high-fat dietary content redirects local immune responses to allergen in the lungs and systemic responses in the spleen and serum. These effects are not due to changes in regulatory T cell populations but may reflect a failure to mobilize eosinophils in response to allergic challenge.
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: A
authors.initials: A
authors.lastname: de Vries
authors.forename: L
authors.initials: L
authors.lastname: Hazlewood
authors.forename: P M
authors.initials: PM
authors.lastname: Fitch
authors.forename: J R
authors.initials: JR
authors.lastname: Seckl
authors.forename: P
authors.initials: P
authors.lastname: Foster
authors.forename: S E M
authors.initials: SE
authors.lastname: Howie
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology*; D004041:Dietary Fats / Q000009:adverse effects* / Q000276:immunology; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000209:etiology / Q000276:immunology*; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D003208:Concanavalin A; D010047:Ovalbumin