Dietary (n-3) polyunsaturated fatty acids affect the kinetics of pro- and antiinflammatory responses in mice with Pseudomonas aeruginosa lung infection.
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-alpha], antiinflammatory markers (IL-10, A20, and IkappaB alpha), and PPARalpha and PPARgamma. 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 PPARalpha and PPARgamma 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.
Tiesset
Hélène
H
EA 3925, Faculty of Medicine, 59045 Lille, France.
Pierre
Maud
M
Desseyn
Jean-Luc
JL
Guéry
Benoît
B
Beermann
Christopher
C
Galabert
Claude
C
Gottrand
Frédéric
F
Husson
Marie-Odile
MO
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051101:Neurturin; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D013995:Time
D015525:Fatty Acids, Omega-3; D051101:Neurturin