Trimethylmethoxyphenyl-retinoic acid (Ro 10-1670) inhibits mitogen-induced DNA-synthesis in peripheral blood lymphocytes in vitro.

Trimethylmethoxyphenyl-retinoic acid (TMMP-retinoic acid, Ro 10-1670) is the main metabolite of the aromatic retinoid Ro 10-9359 (Tigason, etretinate), which is now in clinical use. Therefore, we selected this metabolite for our in vitro studies on human lymphocytes. The following findings were obtained: TMMP-retinoic acid is practically insoluble in aqueous solution. It remains partly in solution only if bound to protein. Under these conditions it had no influence on DNA-synthesis of human peripheral blood lymphocytes added in vitro without lectins (5--12.5 ng/ml culture medium). However, if human peripheral blood lymphocytes were cultured in vitro with lectins (ConA, PHA-M, PHA-P and PWM) and in the presence of TMMP-retinoic acid (25 microgram/ml culture medium) no induction of DNA-synthesis was seen. The altered lymphocytic response in presence of TMMP-retinoid in vitro was clearly dose-dependent at these levels. Trypan blue exclusion tests showed no evidence of cytotoxicity. Our studies clearly indicate that TMMP-retinoic acid inhibits the biological response of human blood lymphocytes to lectins in vitro, at dosages close to therapeutic levels in vivo. They confirm that retinoids may exert distinct effects on dermal cells in addition to their influence on keratinocytes, and suggest that the therapeutic action of the drug may be also related to the altered lymphocytic response.