An orally active Th1/Th2 balance modulator, M50367, suppresses Th2 differentiation of naı̈ve Th cell in vitro

We previously reported an orally active anti-allergic agent, M50367, modulated Th1/Th2 balance to down-regulate Th2 response in a murine model of atopic asthma. In this study, we examined the effect of M50354, the active metabolite of M50367, on the differentiation of naı̈ve Th cells into Th1/Th2 cells. M50354 at 3 μM decreased the generation of Th2 cells by 0.2-fold and increased that of Th1 cells by 1.6-fold from naı̈ve Th cells primed with antigenic peptide and antigen-presenting cells. Its effect was also seen when naı̈ve Th cells were primed with anti-T cell receptor and anti-CD28 agonistic antibodies instead of antigen and antigen-presenting cells. M50354 decreased early endogenous IL-4 production in the naı̈ve Th cell priming culture without affecting interferon-γ production and proliferation. In contrast, M50354 had no effect on interferon-γ and IL-4 production from mature Th1 and Th2 cells. These results suggest that M50354 directly acts on naı̈ve Th cells to suppress their differentiation into Th2 cells.