Cationic lipid/DNA complexes induce TNF-alpha secretion in splenic macrophages

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Caroline LonezJean-Marie Ruysschaert

Abstract

Cationic lipids are widely used as vectors to deliver DNA into mammalian cells in vitro and in vivo. However, cationic lipid/DNA lipoplexes induce an inflammatory response, characterized by pro-inflammatory cytokine secretion, which severely limits their use. The main goal of this work is to identify the organs and the cell type involved in TNF-alpha secretion after lipoplex injection. We determined the kinetics of distribution of the cationic lipid/DNA complex in blood, lung, liver and spleen and quantified the TNF-alpha amount in organ homogenates and in the serum at different points of times. Increase in TNF-alpha production was only observed in the spleen and no significant increase of TNF-alpha production could be observed in the other organs. Fractionation of spleen cells revealed that macrophages were mainly responsible for TNF-alpha secretion. This observation was verified in vivo by using macrophage-removing agents. In conclusion, we show here that the TNF-alpha secreted in the serum after intravenous injection of lipoplexes comes mainly from the splenic macrophages.

Citations

Dec 2, 2011·The Journal of Toxicological Sciences·Shingo OgawaIchiro Fujimoto
Oct 30, 2016·Therapeutic Delivery·Jennifer CheungNejat Düzgünes
Aug 21, 2010·Vascular Medicine·Brian L WaltonGabriel Lopez-Berestein
Mar 28, 2020·International Journal of Molecular Sciences·Marco HoffmannBernd Hoffmann

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