title: Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto SP 14049-900, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Malardo
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Batalhão
authors.forename: Ademilson
authors.initials: A
authors.lastname: Panunto-Castelo
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Almeida
authors.forename: Everton
authors.initials: E
authors.lastname: Padilha
authors.forename: Isabela C
authors.initials: IC
authors.lastname: Fontoura
authors.forename: Célio L
authors.initials: CL
authors.lastname: Silva
authors.forename: Evelin C
authors.initials: EC
authors.lastname: Carnio
authors.forename: Arlete A M
authors.initials: AA
authors.lastname: Coelho-Castelo
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D019446:Endotoxemia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009566:Nitrates / Q000097:blood; D010957:Plasmids / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014667:Vasopressins / Q000097:blood*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D014667:Vasopressins; D004247:DNA