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Nutritional Immunology

A Conjugated Linoleic Acid-Enriched Beef Diet Attenuates Lipopolysaccharide-Induced Inflammation in Mice in Part through PPAR-Mediated Suppression of Toll-Like Receptor 4^1,2,3

⁴ Nutrigenomics Research Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland ⁵ Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland ⁶ Trinity Centre for Health Sciences, St. James Hospital, Dublin 7, Ireland ⁷ Teagasc, Grange Beef Research Centre, Dunsany, County Meath, Ireland ⁸ Immune Regulation Research Group, Trinity College Dublin, Dublin 2, Ireland

Conjugated linoleic acid (CLA) is a PUFA found in beef and dairy products that has immunoregulatory properties. The level of CLA in beef can be enhanced by feeding cattle fresh grass rather than concentrates. This study determined the effect of feeding a high-CLA beef diet on inflammation in an in vivo model of septic shock. Mice were fed a high-CLA beef (4.3% total fatty acid composition) or low-CLA beef diet (0.84% total fatty acid composition) for 6 wk. Lipopolysaccharide (LPS; 3 µg) or sterile PBS was injected i.v. and serum was harvested 6 h after injection. Serum interleukin (IL)-1β, IL-12p70, IL-12p40, and interferon- concentrations were significantly reduced in response to the LPS challenge in the high-CLA beef diet group. Bone marrow-derived dendritic cells (BMDC) from the high-CLA beef diet group had significantly less IL-12 and more IL-10 in response to ex vivo LPS stimulation. Furthermore, toll-like receptor 4 (TLR4) and CD14 protein and mRNA expression on BMDC was significantly attenuated in the high-CLA compared with the low-CLA beef diet group. Complimentary in vitro experiments to determine the specificity of the effect showed that synthetic cis9, trans11-CLA suppressed surface expression of CD14 and TLR4 on BMDC. Treatment with the PPAR inhibitor GW9662 partially reversed TLR4 expression in immature BMDC. The results of this study demonstrate that feeding a diet enriched in high-beef CLA exerts profound antiinflammatory effects in vivo within the context of LPS-induced sepsis. In addition, downregulation of BMDC TLR4 is mediated through induction of PPAR.

^* To whom correspondence should be addressed. E-mail: helen.roche{at}ucd.ie.

Manuscript received 15 July 2009. Initial review completed 9 August 2009. Revision accepted 8 October 2009.