Inhibition of endotoxin-induced lung inflammation by interleukin-10 gene transfer in mice

Citation
S. Dokka et al., Inhibition of endotoxin-induced lung inflammation by interleukin-10 gene transfer in mice, AM J P-LUNG, 279(5), 2000, pp. L872-L877
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN journal
1040-0605 → ACNP
Volume
279
Issue
5
Year of publication
2000
Pages
L872 - L877
Database
ISI
SICI code
1040-0605(200011)279:5<L872:IOELIB>2.0.ZU;2-5
Abstract
Interleukin (IL)-10 is an anti-inflammatory cytokine that has great potenti al for use in the treatment of inflammatory and immune illnesses. In this s tudy, gene transfer was used to induce IL-10 transgene expression in murine lungs for treatment of endotoxin-induced lung inflammation. Gene transfer was performed with a cytomegalovirus (CMV)-IL-10 plasmid with the aid of th e liposomal agents LipofectAMINE and N-[1-(2,3-dioleoyl) propyl]- N,N,N-tri methylammonium methylsulfate (DOTAP). Administration of the endotoxin cause d a marked increase in lung inflammation as indicated by increased tumor ne crosis factor (TNF)-alpha release and neutrophil count. Pretreatment of the mice with IL-10 plasmid with and without LipofectAMINE had no inhibitory e ffect on lung inflammation and IL-10 transgene expression. LipofectAMINE by itself induced lung inflammation, an effect that was not observed with DOT AP. IL-10 plasmid when codelivered with DOTAP expressed biologically active IL-10 protein and caused a reduction in endotoxin-induced inflammation. Tr ansgene expression was observed as early as 3 h after administration, peake d at 12 h, and declined thereafter. We conclude that IL-10 gene transfer is a feasible approach for the treatment of lung inflammation.