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. 2016 Nov;42(7):1522-1527.
doi: 10.1016/j.burns.2016.05.005. Epub 2016 Jun 4.

Direct detection of blood nitric oxide reveals a burn-dependent decrease of nitric oxide in response to Pseudomonas aeruginosa infection

Julia L M Dunn  1 , Rebecca A Hunter  2 , Karli Gast  3 , Robert Maile  4 , Bruce A Cairns  5 , Mark H Schoenfisch  6
Affiliations

Direct detection of blood nitric oxide reveals a burn-dependent decrease of nitric oxide in response to Pseudomonas aeruginosa infection

Julia L M Dunn et al. Burns. 2016 Nov.

Abstract

Purpose: Burn is associated with severe immune dysfunction, including an anti-inflammatory state that occurs late after burn. While increased nitric oxide (NO) production is associated with severe infection and sepsis, the effect of burn trauma on these levels during a non-lethal infection remains unknown. We hypothesized that in a mouse model, (1) NO levels would be increased after infection without trauma and (2) burn would lead to decreased NO production even during infection.

Methods: Mice were infected via intra-tracheal inoculation with Pseudomonas aeruginosa 14 d following a 20% total body surface area contact burn. At 48h following infection, blood was drawn to quantify NO concentrations using a microfluidic electrochemical sensor.

Significant findings: In uninjured mice, infection caused a significant increase in blood NO levels. Increases in NO occurred in a dose-dependent response to the bacterial inoculum. Following burn, an identical infection did not elicit increases in NO.

Conclusions: While increases in NO are expected over the course of an infection without prior trauma, burn and subsequent immune suppression decreases NO levels even in the presence of infection.

Keywords: Burn; Compensatory anti-inflammatory response syndrome; Electrochemistry; Microfluidic sensor; Nitric oxide; Pneumonia; Pseudomonas aeruginosa; Sepsis.

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Figures

Figure 1
Figure 1. Nitric Oxide (NO) levels are elevated following infection without prior injury in a dose-dependent fashion
Mice (n=4) were infected with of P. aeruginosa and blood NO analyzed. A) NO levels were significantly increased 48 h following infection with1 × 106 CFU compared to uninfected counterparts. Statistical significance is indicated by *, p < 0.05 by a Student’s t test. B) NO levels in blood and bacterial recovery from lungs were higher in mice inoculated with 5 × 105 CFU vs. 5 × 106 CFU at 72 hours post infection. Statistical significance is indicated by *, p<0.05 and ***, p < 0.001 by Two-way ANOVA with Bonfennori post-test. Data are given as mean ± standard deviation.
Figure 2
Figure 2. Relative to sham mice, burn injury causes decreased blood NO concentrations and increased pulmonary bacterial load following a 14 d post-burn infection
Mice (n=4) were infected with 1 × 106 CFU of P. aeruginosa 14 d after injury and blood NO analyzed 48 h after infection. Statistical significance is indicated by *, p<0.05 and ***, p < 0.001 by a Two-way ANOVA followed by Bonfennori post-test. Data are given as mean ± standard deviation.
Figure 3
Figure 3. Inoculation dose impacts blood NO concentration in burn mice following infection
Mice (n=3–4) were infected with A) 5 × 105 or B) 5 × 106 CFU of P. aeruginosa and blood NO analyzed after 24 h or 72 h. Statistical significance is indicated by ***, p < 0.001 by a Two-way ANOVA followed by Bonfennori post-test. Data are given as mean ± standard deviation.
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