Effects of Retinoids on in vitro and in vivo IgE Production

Background: Retinoids modulate the growth and number of different cell type s, including B cells. We could previously show that retinoic acid (RA) stro ngly inhibits CD40 + IL-4-mediated IgE production in vitro. The aim of the present study was to extend these findings regarding the potential use of r etinoids for the treatment of allergic diseases. Methods: In vitro IgE prod uction was studied in anti-CD40 + IL-4-stimulated peripheral blood mononucl ear cells (PBMC) from allergic donors in the presence of 10(-15)-10(-5) M a ll-trans and 13-cis RA and in ovalbumin (OVA)-sensitized BALB/c mice treate d with RA (20 mg/kg) before and during sensitization. IgE and IgG1 levels w ere determined in the sera of the mice at day 21 after 2 injections (days 1 and 8) of aluminum hydroxide-absorbed OVA. Results: All-trans and 13-cis R A inhibited in vitro IgE production from PBMC in a dose-dependent manner, b ut were more efficient in atopic dermatitis patients with low total serum I gE levels (< 400 kU/ml), maximal inhibition for all-trans RA at 10(-7) M (8 7%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high seru m IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-c is RA at 10-5 M(53 and 39%, respectively). In contrast, the in vivo data fr om OVA-sensitized mice revealed comparable total IgE and IgG1 levels in con trol versus all-trans RA or CD336-treated groups, specific IgE was even hig her in the CD336-treated group (n = 10, 2,814 ng/ml), and was comparable in mice treated with OVA alone or with additional all-trans RA (n = 10, 1,447 and 1,354 ng/ml, respectively). Conclusions: These results indicate that t he efficacy of retinoids to inhibit IgE production in vitro depends on the frequency of switched cells in the peripheral blood and that in an in vivo model using OVA-sensitized mice, retinoids fail to inhibit IgE production. Copyright (C) 2001 S. Karger AG, Basel.