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

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.