Inhibition of endotoxin-induced lung inflammation by interleukin-10 gene transfer in mice.
Interleukin (IL)-10 is an anti-inflammatory cytokine that has great potential for use in the treatment of inflammatory and immune illnesses. In this study, 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 the liposomal agents LipofectAMINE and N-[1-(2,3-dioleoyl)propyl]-N,N, N-trimethylammonium methylsulfate (DOTAP). Administration of the endotoxin caused a marked increase in lung inflammation as indicated by increased tumor necrosis factor (TNF)-alpha release and neutrophil count. Pretreatment of the mice with IL-10 plasmid with and without LipofectAMINE had no inhibitory effect on lung inflammation and IL-10 transgene expression. LipofectAMINE by itself induced lung inflammation, an effect that was not observed with DOTAP. IL-10 plasmid when codelivered with DOTAP expressed biologically active IL-10 protein and caused a reduction in endotoxin-induced inflammation. Transgene expression was observed as early as 3 h after administration, peaked at 12 h, and declined thereafter. We conclude that IL-10 gene transfer is a feasible approach for the treatment of lung inflammation.
Dokka
S
S
Department of Pharmaceutical Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506, USA.
Malanga
C J
CJ
Shi
X
X
Chen
F
F
Castranova
V
V
Rojanasakul
Y
Y
D000818:Animals; D002411:Cation Exchange Resins; D003587:Cytomegalovirus; D004731:Endotoxins / Q000633:toxicity; D005229:Fatty Acids, Monounsaturated; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007249:Inflammation / Q000139:chemically induced / Q000628:therapy*; D016753:Interleukin-10 / Q000235:genetics* / Q000502:physiology; D008055:Lipids; D008070:Lipopolysaccharides / Q000633:toxicity*; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D000644:Quaternary Ammonium Compounds
D002411:Cation Exchange Resins; D004731:Endotoxins; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; C086724:Lipofectamine; D008070:Lipopolysaccharides; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D016753:Interleukin-10; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane