Inhibition of IgE production by the imidazoquinoline resiquimod in nonallergic and allergic donors

The aim of this study was to examine whether the immune modulator resiquimod, which belongs like imiquimod to the imidazoquinolines, is capable of influencing IgE synthesis. Peripheral blood mononuclear cells from normal donors and patients with atopic dermatitis and with seasonal allergic rhinitis were analyzed in the presence of resiquimod, anti-CD40 + interleukin-4 stimulation for induction of IgE, and anti-CD40 + interleukin-4 in the presence of resiquimod, respectively. Our data show that spontaneous IgE production was inhibited in the presence of resiquimod, which was strongest at 10 ng per ml in both groups of allergic patients. Inhibition of IgE production after anti-CD40 + interleukin-4 stimulation in the presence of resiquimod (10 ng per ml) was comparable between all the groups. In normal donors median inhibition of IgE synthesis was 93%, in seasonal allergic rhinitis patients 77%, and in patients with atopic dermatitis 72%. In order to rule out antiproliferative effects of resiquimod, which might influence IgE production, we also studied proliferation of peripheral blood mononuclear cells from normal donors, which remained unchanged in the presence of resiquimod at 0.1-10 ng per ml but was inhibited at 100 or 1000 ng per ml. In search of possible mechanisms responsible for the observed inhibition of IgE production, we analyzed the expression and production of molecules that are known to modulate IgE production, namely CD23 and interferon-gamma. CD23 expression on B cells was lower in the presence of resiquimod (10 ng per ml) in anti-CD40 + interleukin-4 stimulated cells, whereas interferon-gamma was strongly induced (4-6-fold) by resiquimod (10 ng per ml). Furthermore, by using neutralizing interferon-gamma monoclonal antibodies, we show that inhibition of IgE production occurred in an interferon-gamma-dependent manner. Taken together our results show that resiquimod is a potent modulator of IgE production in vitro in normal but also in allergic donors.