Effects of retinoic acid (vitamin A) on tumor necrosis factor cytolytic action

Tumor necrosis factor (TNF) is a monokine produced primarily by macrophages. TNF has a number of activities including direct lysis of certain transformed cells and induction of antiviral activity. One of the protoypical transformed cell lines used for studying TNF cytolysis is murine L-929 cells. Because of the lysis, TNF has not been shown to have antiviral activity in these cells. Since retinoic acid (RA) induces a normal phenotype in the L-929 cells, we sought to determine if their conversion to a normal phenotype would 1) render them insensitive to the cytolytic effect and 2) allow for the development of an antiviral state. We present evidence that both the cis- and trans- forms of RA and to a lesser extent, the RA precursor beta-carotene, can inhibit recombinant human TNF cytolytic activity in mouse L-929 cells. However, blockage of the cytolytic activity does not allow development of an antiviral state.