Vitamin A and retinoic acids immunomodulation on human gut lymphocytes

Epidemiological studies have suggested an important immunomodulatory role for vitamin A and other related vitamin A compounds in adults and children. Although vitamin A is absorbed via the gastrointestinal tract, its affect on the gut mucosal immune cells has not been adequately investigated. We investigated the in-vitro effect of vitamin A (retinol) and its retinoid acid (RA) compounds (13-cis- and all trans-retinoic acids) on the human gut mucosal immune system as represented by colonic lamina propria lymphocyte (LPL) proliferation, and ornithine decarboxylase (ODC) activity. Results showed that retinol suppressed and trans-retinoic acid enhanced thymidine incorporation into LPL. 13-cis retinoic acid did not significantly affect LPL DNA synthesis. Similarly, retinol (0.025 microgram/ml and 10 micrograms/ml) and 13-cis retinoic acid (conc. 10 micrograms/m) suppressed, while all trans-retinoic acid (conc. 10 micrograms/ml) enhanced ODC activity in PHA-stimulated LPL. Interestingly, the effects of retinol and all trans-RA were abolished when LPL were previously depleted of macrophages. Addition of monocyte-associated lymphokines, IL-1 and IL-6, showed that IL-1 partially replaced the enhancing effect of all trans-RA previously observed on LPL thymidine incorporation. IL-6 did not affect LPL DNA synthesis irrespective of the vitamin A compound used. We conclude that retinol and retinoid acids (13-cis, all trans-) may alter the human colonic immune system possibly via IL-1 cytokine, but not via IL-6. The data suggest that vitamin A and its retinoid compounds may participate in the modulation of the gut immune system.