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Clinical & Experimental Allergy

High-fat feeding redirects cytokine responses and decreases allergic airway eosinophilia

Authors

  • A. De Vries,

    1. MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh,
    2. Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
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    • 1Current address: TMRC Lab, Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

  • L. Hazlewood,

    1. Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, Australia
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  • P. M. Fitch,

    1. MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh,
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  • J. R. Seckl,

    1. Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
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  • P. Foster,

    1. Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, Australia
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  • S. E. M. Howie

    1. MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh,
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Correspondence:
Professor Sarah Howie, Immunity and Chronic Inflammation Group, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. E-mail: s.e.m.howie@ed.ac.uk

Summary

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-α) 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-γ 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.

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