(n-3) Long-Chain PUFA Differentially Affect Resistance toPseudomonas aeruginosaInfection of Male and Femalecftr–/–Mice

The aim of this study was to determine whether oral supplementation with EPA/DHA (10.5 and 5.1% of fat, respectively) could improve the outcome of pulmonaryP. aeruginosainfection incftr–/–mice compared with wild-type (Wt) mice similarly treated. Because gender could influence the susceptibility ofcftr-deficient mice, results were analyzed by gender. Wt and–/–mice were randomized for 6 wk to consume a control or EPA/DHA diet, infected with endotracheal injection of 5 × 107CFU/mouse ofP. aeruginosa, and killed 24 h later.Cftr–/–mice were more susceptible to infection than were Wt mice;–/–males had more neutrophils (P <0.01) and a higher keratinocyte-derived chemokine (KC) level (P <0.05), and–/–females had greater lung injury and mortality (P <0.05). Female–/–mice were more susceptible than–/–males with a higher mortality and lung injury(P< 0.05). The EPA/DHA diet reduced neutrophil numbers and KC and IL-6 levels (P <0.05) in–/–males and reduced mortality rate (P <0.001), lung permeability, and IL-6 level(P< 0.05) in–/–females compared with–/–mice fed the control diet. These results were associated with a reduction in the pulmonary bacterial load (P <0.05), an increase in the EPA/DHA concentration in cell membranes of–/–males and females(P <0.01), and an increased weight gain only in males compared wit–/–mice fed the control diet(P <0.01). In conclusion, EPA/DHA improves the host resistance of–/–mice, although the beneficial effect differed in males and females.