Bacterial translocation is inhibited in inducible nitric oxide synthase knockout mice after endotoxin challenge but not in a model of bacterial overgrowth.
BACKGROUND
Studies have shown that nitric oxide (NO) and NO synthase (NOS) inhibitors injure and protect organs after endotoxin (lipopolysaccharide [LPS]) challenge.


OBJECTIVE
To test the hypothesis that LPS-induced gut injury and bacterial translocation (BT) are mediated through activation of inducible NOS (iNOS).


METHODS
A randomized, controlled study using genetically altered, iNOS gene knockout mice.


METHODS
University research laboratory.


METHODS
Forty-five wild-type (iNOS+/+) or homozygous mutant (iNOS-/-) mice weighing 25 to 35 g were challenged with Escherichia coli LPS or saline (10 mg/ kg) intraperitoneally (n = 8/group). In a second set of experiments, a bacterial overgrowth model of BT (E coli monoassociation) was tested (n = 6-7/group). The mesenteric lymph nodes and cecums were cultured, and liver, ileal, and blood nitrite and nitrate levels measured 24 hours after LPS or E coli monoassociation.


RESULTS
After LPS challenge, 87.5% of the iNOS+/+ mice but 0% of the iNOS-/- mice had BT to their mesenteric lymph nodes (P < .01; chi 2 analysis). Nitrite and nitrate levels of the liver, ileum, and blood were higher in the iNOS+/+ mice (P < .05). In the E coli overgrowth model, BT to mesenteric lymph nodes occurred in 100% of iNOS-/- and iNOS+/+ mice.


CONCLUSIONS
In this limited study, LPS-induced BT did not occur in iNOS-deficient mice, suggesting that LPS induction of increased iNOS activity is necessary for LPS-induced BT to occur. In contrast, iNOS activation does not seem to be necessary in a bacterial overgrowth model of BT.
Mishima
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Department of Surgery, UMDNJ-New Jersey Medical School, Newark, USA.
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Deitch
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D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000502:physiology*
D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase