Inhibition of IgE-Production by Peroxisome Proliferator-Activated Receptor Ligands

Abstract

In this study we analyzed the effect of peroxisome proliferator-activated receptor-alpha and -gamma ligands on immunoglobulin synthesis and cytokine production in non-allergic and atopic dermatitis donors in vitro, but also in vivo ovalbumin-sensitized mice. A significant inhibition in CD40+ interleukin-4-mediated, but also basal IgE synthesis from peripheral blood mononuclear cells of atopic dermatitis donors was observed in the presence of the peroxisome proliferator-activated receptor-alpha ligand (up to 47+/-12%) and peroxisome proliferator-activated receptor-gamma ligand (69+/-5%). By contrast, the production of other isotypes such as IgA, IgG, and IgM was only modest inhibited. Analysis of cytokine production from the peripheral blood mononuclear cells shows inhibition of several cytokines by both peroxisome proliferator-activated receptor ligands. The most inhibitory effect on cytokine production was observed by the peroxisome proliferator-activated receptor-gamma ligand in peripheral blood mononuclear cells from atopic dermatitis donors with high IgE baseline production. Coculture experiments show that the decrease of IgE production by ciglitazone was monocyte dependent (up to 63+/-7%). Finally, in vivo experiments from ovalbumin-sensitized mice confirmed the in vitro findings showing that the interleukin-4-mediated immune response was inhibited in ciglitazone-treated mice.