Expression Of Low-affinity Receptor For IgE Research Articles

Suppression of IgE Production by IPD-1151T (Suplatast Tosilate), a New Dimethylsulfonium Agent: (1) Regulation of Murine IgE Response

The effect of IPD-1151T, a new dimethylsulfonium compound, on the IgE response was investigated in the mouse system. The oral administration of IPD-1151T to immunized BALB/c mice suppressed the primary IgE antibody response and depressed the elevation of serum IgE levels, whereas the same treatment did not affect the IgG antibody response. The enhanced expression of low-affinity IgE receptor (Fc ε RII/CD23) on the spleen cells of immunized mice was also inhibited by IPD-115 IT administration. It was further demonstrated from the adoptive transfer experiment that IPD-115IT, administered to hapten-primed B cell donors, but not to carrier-primed T cell donors, exerted its suppressive influence on the hapten-specific secondary IgE antibody response in irradiated syngeneic recipients. Interestingly, IPD-1151T concentration-dependently inhibited the production of interleukin 4 (IL-4) by D10G4.1, known to be a typical Th2 clone. However, IPD-1151T did not suppress the production of IgE and IgGl by normal splenic B cells stimulated with lipopolysaccharide and IL-4. Moreover, IL-4-induced expression of Fc ε RII on normal spleen cells was not inhibited by the agent. These results strongly suggest that the IgE-suppressive activity of IPD-115IT is most likely due to the inhibition of IL-4 production at the T cell level.

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-115IT induced a concentration-dependent suppression of purified allergen (Cry j 1)-ndependent 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-115IT had no antagonistic action on IL-4, since neither IL-4-induced expression of low-affinity IgE receptor (Fc ε RII/CD23) on normal B cells nor soluble Fc ε 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-γ 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-115 IT results from the inhibition of IL-4 production by T cells at the gene level.