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

Abstract

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. 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. 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. 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.