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

Dokka S; Malanga CJ; Shi X; Chen F; Castranova V; Rojanasakul Y

Am J Physiol, Lung Cell Mol Physiol 2000 Nov; 279(5):L872-L877

https://doi.org/10.1152/ajplung.2000.279.5.L872

20020654

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.

Endotoxins; Laboratory animals; Animals; Animal studies; Lung disorders; Lung irritants; Pulmonary system disorders; Respiratory system disorders; Author Keywords: tumor necrosis factor-a; gene transfer; liposome

Y. Rojanasakul, West Virginia University School of Pharmacy, Department of Basic Pharmaceutical Sciences, PO Box 9530, Morgantown, WV 26506

APLPE7

20001101

Journal Article

yrojanasakul@hsc.wvu.edu

2001

5

1040-0605

HELD

American Journal of Physiology: Lung Cellular and Molecular Physiology

WV