Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia

• Main Authors: Malardo Thiago, Batalhão Marcelo E, Panunto-Castelo Ademilson, Almeida Luciana P, Padilha Everton, Fontoura Isabela C, Silva Célio L, Carnio Evelin C, Coelho-Castelo Arlete AM
• Format: Article
• Language: English
• Published: BMC 2012-11-01
• Series: BMC Immunology
• Subjects: Endotoxemic shock; Interleukin-6; Naked pcDNA3
• Online Access: http://www.biomedcentral.com/1471-2172/13/59

<p>Abstract</p> <p>Background</p> <p>Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert) as therapeutic agent requires further investigation.</p> <p>Results</p> <p>Here, we showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and TNF-α by lipopolysaccharide (LPS)-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 μg of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP) drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP), a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO) production.</p> <p>Conclusion</p> <p>Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases.</p>