EFFECT OF RU-38486 ON TNF PRODUCTION AND TOXICITY

Glucocorticoid steroids provide considerable protection against the systemic toxicity of tumor necrosis factor-alpha (TNF-alpha, cachexin). In animal experiments RU 38486 (mifepristone), a steroid antagonist, increased the synthesis of TNF and sensitized the animals to the cytotoxic action of TNF. As compared to the control and methylprednisolone-treated groups, mifepristone significantly increased the level of TNF in the serum, liver and spleen of lipopolysaccharide (LPS)-treated animals. In tissue cultures RU 38486 induced the TNF synthesis of myeloid cells and increased the TNF production of genetically modified HeLa cells, which synthesize TNF constitutively. Normal and tumor cell cultures exhibited increased sensitivity toward TNF in the presence of mifepristone.