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Infection and Immunity, March 2004, p. 1479-1486, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1479-1486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Nutritional Effects on Host Response to Lung Infections with Mucoid Pseudomonas aeruginosa in Mice

Anna M. van Heeckeren,1* Mark Schluchter,1 Lintong Xue,1 Juan Alvarez,2,3 Steven Freedman,3 Judith St. George,4 and Pamela B. Davis1

Case Western Reserve University School of Medicine, Cleveland, Ohio,1 Hospital San Rafael, La Coruña, Spain,2 Harvard Medical School, Boston,3 Genzyme Corporation, Framingham, Massachusetts4

Received 3 November 2003/ Returned for modification 4 December 2003/ Accepted 11 December 2003

In cystic fibrosis, a recessive genetic disease caused by defects in the cystic fibrosis conductance regulator (CFTR), the main cause of death is lung infection and inflammation. Nutritional deficits have been proposed to contribute to the excessive host inflammatory response in both humans and Cftr-knockout mice. Cftr-knockout mice and gut-corrected Cftr-knockout mice expressing human CFTR primarily in the gut were challenged with Pseudomonas aeruginosa-laden agarose beads; they responded similarly with respect to bronchoalveolar lavage cell counts and levels of the acute-phase cytokines tumor necrosis factor alpha, interleukin-1ß (IL-1ß), and IL-6. Wild-type mice fed the liquid diet used to prevent intestinal obstruction in Cftr-knockout mice had inflammatory responses to P. aeruginosa-laden agarose beads similar to those of wild-type mice fed an enriched solid diet, so dietary effects are unlikely to account for differences between wild-type mice and mice with cystic fibrosis. Finally, since cystic fibrosis patients and Cftr-knockout mice have an imbalance in fatty acids (significantly lower-than-normal levels of docosahexaenoic acid), the effects of specific supplementation with docosahexaenoic acid of wild-type and Cftr-knockout mice on their inflammatory responses to P. aeruginosa-laden agarose beads were tested. There were no significant differences (P = 0.35) in cumulative survival rates between Cftr-knockout mice and wild-type mice provided with either the liquid diet Peptamen or Peptamen containing docosahexaenoic acid. In conclusion, diet and docosahexaenoic acid imbalances alone are unlikely to explain the differences in the host response to lung infections with mucoid P. aeruginosa between mice with cystic fibrosis and their wild-type counterparts.


* Corresponding author. Mailing address: Case Western Reserve University School of Medicine, Biomedical Research Building 827, 2109 Adelbert Rd., Cleveland, OH 44106-4948. Phone: (216) 368-0008. Fax: (216) 368-4223. E-mail: anna.vanheeckeren{at}cwru.edu.

Editor: J. N. Weiser


Infection and Immunity, March 2004, p. 1479-1486, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1479-1486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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