Modulation of human immune functions in vitro by temarotene and its metabolite.

The arotinoid temarotene (Ro 15-0778) and its metabolite Ro 14-6113 were examined in a variety of in vitro assays quantitating parameters of human immune functions. Both immunosuppressive and immunostimulatory activities of these compounds were identified. These activities were compared with those of the known immunomodulatory compound ciclosporin A (CsA) at concentrations corresponding to clinically effective plasma concentrations. Like CsA, Ro 14-6113 inhibited the mitogen- or alloantigen-induced proliferation of T cells as well as their capacity to secrete interleukin-2 (IL-2), interferon-gamma and tumor necrosis factor alpha. Ro 15-0778 showed no activity in inhibiting cytokine secretion and was considerably less effective than Ro 14-6113 in inhibiting T cell proliferation. Ro 14-6113 was more effective than CsA in inhibiting IL-2 receptor expression. Ro 14-6113 modulated both positively or negatively the proliferation of B cells, depending on the concentration. Ro 14-6113 inhibited the secretion of IgM, IgG, and IgA, while stimulating IgE secretion. A different profile of activity for Ro 14-6113 and CsA was observed, suggesting differing effectiveness in immunologically mediated diseases.