Immunomodulatory Activity of Synthetic Triterpenoids: Inhibition of Lymphocyte Proliferation, Cell-Mediated Cytotoxicity, and Cytokine Gene Expression Through Suppression of NF-κB

Abstract

Synthetic oleanane triterpenoids (CDDO, CDDO-Im and CDDO-Me) are potent anti-inflammatory agents, but have not been investigated for effects on T cell-mediated immune responses. Here we demonstrate that CDDOs have profound immunosuppressive effects on T cell proliferation, development of IL-2 activated LAK cells and cytotoxic T lymphocytes (CTLs), and expression of cytokines at concentrations of 1.25 μM to 0.078 μM. Treatment with CDDO-Me also inhibited the generation of allo-reactive T cell responses in vivo. The suppression of these cell-mediated immune responses by CDDO-Me was associated with the inhibition of NF-κB transcription factor.