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Nutrition and Disease

Dietary (n-3) Polyunsaturated Fatty Acids Affect the Kinetics of Pro- and Antiinflammatory Responses in Mice with Pseudomonas aeruginosa Lung Infection^1,2,3

⁴ EA 3925, Faculty of Medicine, 59045 Lille, France ⁵ IMPRT/IFR 114, 59045 Lille, France ⁶ University of Lille 2, 59045 Lille, France ⁷ INSERM U837-JPARC, 59045 Lille cedex, France ⁸ EA 2689, Faculty of de Medicine, 59045 Lille, France ⁹ Danone Research, Center of Specialized Nutrition,D-61276 Friedrichsdorf, Germany and Food Technology, University of Applied Science Fulda, D-36039 Fulda, Germany ¹⁰ CERM, Hospital Renée-Sabran, CHRU Lyon, 83406 Giens-Hyères, France

The underlying mechanisms by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect host resistance to Pseudomonas aeruginosa are unclear. The aim of this study was to determine their role on the kinetic of pro- and antiinflammatory response in lung infection. Mice fed either a control diet or a diet enriched with EPA and DHA were infected intratracheally and we studied lung expression of proinflammatory markers [CXCL1, interleukin (IL)-6, tumor necrosis factor-], antiinflammatory markers (IL-10, A20, and IB), and PPAR and PPAR. The inflammatory response was assessed using recruitment of neutrophils and macrophages into bronchoalveolar lavage fluid, bacterial clearance from the lung, pulmonary injury, and 7-d survival rate. Compared with the control group, EPA and DHA delayed the expression of proinflammatory markers during the first 2 h (P < 0.05), upregulated proinflammatory marker expression (P < 0.05), and induced overexpression of antiinflammatory markers at 8 h (P < 0.05), enhanced recruitment of neutrophils at 16 h (P < 0.05), and induced PPAR and PPAR overexpression at 4 and 8 h (P < 0.01), respectively. Pulmonary bacterial load decreased and pulmonary injury and mortality were reduced during the first 24 h (P < 0.05). In conclusion, EPA and DHA modulate the balance between pro- and antiinflammatory cytokines, alter the early response of the host to P. aeruginosa infection, and affect the early outcome of infection.

^* To whom correspondence should be addressed. E-mail: mohusson{at}chru-lille.fr.

Manuscript received 9 July 2008. Initial review completed 4 August 2008. Revision accepted 17 October 2008.