Omega-3 polyunsaturated fatty acids improve host response in chronic Pseudomonas aeruginosa lung infection in mice

1 Faculté de Médecine and 2 Clinique de Pédiatrie, Hôpital Jeanne de Flandre, Université de Lille and CHRU de Lille, France; 3 JPARC Research Centre, Institut National de la Santé et de la Recherche Médicale, IMPRT, Place de Verdun, Lille, France; 4 CERM, Hôpital Renée Sabran, Giens, Hyères, CHRU Lyon, France; 5 Lipids Research Division, Numico Research, Friedrichsdorf, Germany; 6 Centre de Recherche, Centre Hospitalier de l'Université de Montréal/Hôtel Dieu, Département de Médecine, Université de Montréal, Montréal, Québec, Canada; 7 Centre National de la Recherche Scientifique and 8 Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, France Submitted 30 August 2006 ; accepted in final form 18 February 2007 Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 ( -3) or -6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the -3 diet had a higher lean body mass gain and a lower -6: -3 ratio of fatty acids extracted from the lung tissue compared with the other groups ( P < 0.05). The -3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the -3 group on the 4th day. The effect on DAFC was independent of -epithelial Na + channels ( -ENaC), -ENaC, and 1 -Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in -3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the -6/ -3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients. alveolar liquid clearance Address for reprint requests and other correspondence: B. P. Guery, EA 2689, Faculté de Médecine, Physiologie, 1 Place de Ver