Suppression of IgE production by IPD-1151T (suplatast tosilate), a new dimethylsulfonium agent: (2). Regulation of human IgE response

The ability of IPD-1151T to suppress the induction of human IgE synthesis was investigated with an in vitro model of IgE production mediated by an allergen-specific helper T cell line (SN-4) from a patient allergic to Japanese cedar pollen. IPD-1151T induced a concentration-dependent suppression of purified allergen (Cry j 1)-dependent IgE synthesis in autologous B cell cultures mediated by SN-4, without significantly affecting the IgG synthesis. In addition, the production of interleukin 4 (IL-4) by Cry j 1-activated SN-4 as well as that by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of normal donors was inhibited in a concentration-dependent manner by the agent. Interestingly, IPD-1151T clearly depressed PHA-induced expression of IL-4 mRNA in normal PBMC, indicating that this agent inhibits IL-4 gene transcription. However, IPD-1151T had no antagonistic action on IL-4, since neither IL-4-induced expression of low-affinity IgE receptor (Fc epsilon RII/CD23) on normal B cells nor soluble Fc epsilon RII release from IL-4-stimulated B cells was affected by the agent. On the other hand, IPD-1151T had no effect on the production of interferon-gamma by both Cry j 1-stimulated SN-4 and anti-CD3 monoclonal antibody-activated T cells of normal donors. These results suggest that the selective suppression of IgE synthesis by IPD-1151T results from the inhibition of IL-4 production by T cells at the gene level.