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

In this ex vivo, rather than in vitro, experiment, a synthetic antisense ol igodeoxynucleotide 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 secreti on of TNF at concentrations of 1.0 and 10 mu M. At the concentration of 1 m u M, there were 68.4 and 63.9% suppression of TNF secretion at 2 and 24 h a fter resuspension of blood cells. At the concentration of 10 mu M, the supp ressions were slightly higher than those at 1 mu M, which were 71.8 and 76. 2%, respectively. A 50%-matched scrambler showed suppressive effect only at 10 mu M concentration, and the suppression only occurred at 2 and 24 h aft er incubation. Sense oligomer showed no suppressive effects at any of the c oncentrations. The specificity of this oligomer was documented by dose-effe ct 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 tes ted had no effect on the interleukin-6 secretion after LPS stimulation. In conclusion, properly designed antisense oligodeoxynucleotide can signifi cantly 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 th at are caused by over production of TNF. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved .