Effects of retinoids on in vitro and in vivo IgE production.
BACKGROUND
Retinoids modulate the growth and number of different cell types, including B cells. We could previously show that retinoic acid (RA) strongly 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 retinoids for the treatment of allergic diseases.


METHODS
In vitro IgE production was studied in anti-CD40 + IL-4-stimulated peripheral blood mononuclear cells (PBMC) from allergic donors in the presence of 10(-15)-10(-5) M all-trans and 13-cis RA and in ovalbumin (OVA)-sensitized BALB/c mice treated with RA (20 mg/kg) before and during sensitization. IgE and IgG1 levels were 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 RA inhibited in vitro IgE production from PBMC in a dose-dependent manner, but were more efficient in atopic dermatitis patients with low total serum IgE levels (< 400 kU/ml), maximal inhibition for all-trans RA at 10(-7) M (87%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high serum IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-cis RA at 10(-5) M (53 and 39%, respectively). In contrast, the in vivo data from OVA-sensitized mice revealed comparable total IgE and IgG1 levels in control versus all-trans RA or CD336-treated groups, specific IgE was even higher 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 the 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.
Worm
M
M
Department of Dermatology, Charité-Virchow Klinikum, Humboldt Universität Berlin, Germany. margitta.worm@charite.de
Herz
U
U
Krah
J M
JM
Renz
H
H
Henz
B M
BM
D000485:Allergens / Q000276:immunology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D015474:Isotretinoin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012176:Retinoids / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D000485:Allergens; D001565:Benzoates; D019013:CD40 Antigens; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C068073:Am 580; D015847:Interleukin-4; D007073:Immunoglobulin E; D014212:Tretinoin; D010047:Ovalbumin; D015474:Isotretinoin