Suppression of tumor necrosis factor secretion from white blood cells by synthetic antisense phosphorothioate...

In this ex vivo, rather than in vitro, experiment, a synthetic antisense oligodeoxynucleotide was tested to suppress tumor necrosis factor - alpha(TNF) secretion from lipopolysaccharide-stimulated white blood cells. Antisense oligomer showed significant and specific suppressive effect to the secretion of TNF at concentrations of 1.0 and 10 microM. At the concentration of 1 microM, there were 68.4 and 63.9% suppression of TNF secretion at 2 and 24 h after resuspension of blood cells. At the concentration of 10 microM, the suppressions were slightly higher than those at 1 microM, which were 71.8 and 76.2%, respectively. A 50%-matched scrambler showed suppressive effect only at 10 microM concentration, and the suppression only occurred at 2 and 24 h after incubation. Sense oligomer showed no suppressive effects at any of the concentrations. The specificity of this oligomer was documented by dose-effect phenomenon, sequence-dependent suppression and absence of effect on the synthesis of another cytokine (interleukin-6). A series of parallel studies was performed and showed that all three oligomers at any concentration tested had no effect on the interleukin-6 secretion after LPS stimulation.In conclusion, properly designed antisense oligodeoxynucleotide can significantly and specifically suppress the secretion of TNF by blood cells in an ex vivo system and it may be a good "information" drug to treat diseases that are caused by over production of TNF.