Retinoic acid and other retinoids stimulate or inhibit a number of immune responses, but their mechanism of action on immune cells is not fully understood. However, retinoids have been shown to inhibit interferon production, so they could act by influencing the production of lymphokines. Hence we have studied the effect of retinoic acid on the production of interleukins (ILs) 1 and 3 in vitro. Models for the production of ILs were the murine macrophage cell line P388D1 and human peripheral blood mononuclear cells for IL 1 and the murine WEHI-3 cell line for IL 3. Retinoic acid stimulated IL 1 release by P388D1 cells in a dose-related fashion, starting at 10(-9) M and maximally at 10(-8)-10(-6) M. With peripheral blood mononuclear cells a maximal stimulation of IL 1 release was observed with 10(-7) M-retinoic acid. IL 3 release by WEHI-3 cells was also stimulated by retinoic acid in a dose-related fashion. The maximal response was obtained with 10(-8) M-retinoic acid. These results show that retinoic acid, in physiological concentrations, exerts selective effects on interleukin production in vitro, and this stimulation of IL 1 and IL 3 release may explain some of the immunostimulatory effects of retinoids in vivo. Moreover, since IL 1 is known to influence connective tissues and bone, an increase in IL 1 might also explain some of the changes observed in these tissues in vitamin A poisoning and with high-dose retinoid therapy.

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