Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Baumhofer, J.M. et al.

Gene transfer with IL-4 and IL-13 improves survival in lethal endotoxemia in the mouse and ameliorates peritoneal macrophages immune competence.

Systemic anti-cytokine therapies have been unsuccessful in preventing mortality from gram-negative bacteremia in humans partly because of the failure to neutralize pro-inflammatory cytokines at sites of exaggerated production. In an attempt to deliver anti-inflammatory cytokines to organs directly, gene transfer was employed. Thirty-six BALB/c mice were injected intraperitoneally with cationic liposomes containing plasmids encoding the human interleukin-4 (hIL-4) or IL-13 gene. Both, hIL-4 and hIL-13 mRNA were detected by reverse transcription-polymerase chain reaction analysis in the liver and the spleen of the animals. Fourty-eight hours after the in vivo gene transfer, these 36 mice and 18 mock-transfected mice, were challenged with a lethal dose of E. coli lipopolysaccharide with D-galactosamine (D-GalN). Gene transfer with hIL-4 reduced the serum tumor necrosis factor (TNF)-alpha production in response to endotoxin/D-GalN by 80% from 113.1 pg/ml in mock-transfected animals to 22.2 pg/ml (p < 0.05); human IL-13 gene transfer reduced serum TNF-alpha levels by 90% (113.1 pg/ml to 11.6 pg/ml; p < 0.05). Survival was improved from 20% to over 83% in both treatment groups (p < 0.001). Our data demonstrate a potent in vivo anti-inflammatory action of both IL-4 and IL-13. In addition, the immune functions of peritoneal macrophages are significantly ameliorated in both treatment groups, with IL-13 demonstrating better macrophage immune modulation than IL-4 (p < 0.05).[1]

References

Gene transfer with IL-4 and IL-13 improves survival in lethal endotoxemia in the mouse and ameliorates peritoneal macrophages immune competence. Baumhofer, J.M., Beinhauer, B.G., Wang, J.E., Brandmeier, H., Geissler, K., Losert, U., Philip, R., Aversa, G., Rogy, M.A. Eur. J. Immunol. (1998) [Pubmed]

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