EFFECTS OF RETINOIC ACID (VITAMIN-A) ON TUMOR-NECROSIS-FACTOR CYTOLYTIC ACTION

Tumor necrosis factor (TNF) is a monokine produced primarily by macrop hages. TNF has a number of activities including direct lysis of certai n transformed cells and induction of antiviral activity. One of the pr otoypical transformed cell lines used for studying TNF cytolysis is mu rine 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 t he cytolytic effect and 2) allow for the development of an antiviral s tate. We present evidence that both the cis- and trans- forms of RA an d to a lesser extent, the RA precursor beta-carotene, can inhibit reco mbinant human TNF cytolytic activity in mouse L-929 cells. However, bl ockage of the cytolytic activity does not allow development of an anti viral state. (C) 1995 Academic Press, Inc.