VITAMIN-A INHIBITS CYTOKINES PRODUCED BY TYPE-1 LYMPHOCYTES IN-VITRO

The effect of vitamin A (retinol) on cell-mediated immune responses wa s studied. As an experimental model, Leishmania major infection in mic e was used. In this model, resistant mouse strains develop a type 1 re sponse, while susceptible strains develop a type 2 response. Using lym ph node cells and T-cell lines developed from infected susceptible and resistant mice, it was found that vitamin A inhibited lymphocyte prol iferation in a dose-dependent manner. By separately incubating antigen -presenting cells and T cells with vitamin A, it was shown that the in hibitory effect was on the T cells. Type 1 cytokine (IFN-gamma, GM-CSF , IL-2) secretion in vitro in response to stimulation with specific an tigen 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 Th e inhibitory effect was also observed in PMA-stimulated (but not Con A -stimulated) lymphocytes and was noticeable even if the vitamin was ad ded as late as 24 h after initiation of the incubation period. Since P MA does not operate via a receptor-coupled signaling pathway but rathe r directly affects the protein kinase C (PKC) pathway, we have measure d the effect of vitamin A on PKC in situ activation. Incubation of lym phocytes and antigen in the presence of vitamin A caused inhibition of PKC isoenzymes translocation to the particulate cell fraction, as mea sured by immunoblotting. The results presented indicate that, when add ed to cell cultures in vitro, vitamin A inhibits only secretion of typ e 1 but not type 2 cytokines, possibly through an inhibitory effect on protein kinase C activity. (C) 1998 Academic Press.