Vitamin A inhibits cytokines produced by type 1 lymphocytes in vitro

The effect of vitamin A (retinol) on cell-mediated immune responses was studied. As an experimental model, Leishmania major infection in mice was used. In this model, resistant mouse strains develop a type 1 response, while susceptible strains develop a type 2 response. Using lymph node cells and T-cell lines developed from infected susceptible and resistant mice, it was found that vitamin A inhibited lymphocyte proliferation in a dose-dependent manner. By separately incubating antigen-presenting cells and T cells with vitamin A, it was shown that the inhibitory effect was on the T cells. Type 1 cytokine (IFN-gamma, GM-CSF, IL-2) secretion in vitro in response to stimulation with specific antigen was also inhibited in a dose-dependent manner, whereas secretion of type 2 cytokines (IL-4 and IL-10) was not affected by vitamin A. The inhibitory effect was also observed in PMA-stimulated (but not Con A-stimulated) lymphocytes and was noticeable even if the vitamin was added as late as 24 h after initiation of the incubation period. Since PMA does not operate via a receptor-coupled signaling pathway but rather directly affects the protein kinase C (PKC) pathway, we have measured the effect of vitamin A on PKC in situ activation. Incubation of lymphocytes and antigen in the presence of vitamin A caused inhibition of PKC isoenzymes translocation to the particulate cell fraction, as measured by immunoblotting. The results presented indicate that, when added to cell cultures in vitro, vitamin A inhibits only secretion of type 1 but not type 2 cytokines, possibly through an inhibitory effect on protein kinase C activity.