Biomolecular Regulation Of The Ige Immune-Response .2. In-Vitro Ige Synthesis And Spontaneous Production Of Cytokines

Distinct subtypes of T-helper cells have been incriminated as sources of a common regulatory mechanism behind IgE synthesis and eosinophil activation in IgE-mediated diseases. To investigate whether IgE-producing cells are in fact stimulated in vivo or have an increased susceptibility to certain stimuli, the in vitro IgE synthesis was compared for different patient groups. Peripheral blood mononuclear cells (PBMC) were isolated from three groups of donors: (1) patients with atopic dermatitis and high levels of serum IgE (> 5000 IU/ml, n = 11); (2) patients with diagnosed inhalant allergy and serum IgE in the range of 200-2,000 IU/ml (n=10), and (3) nonallergic donors with serum IgE below 100 IU/ml (n = 10). PBMC were tested for the spontaneous and IL-4-induced IgE synthesis in Ii-day cultures during which adhering cells were removed on day 2 by transferring the suspended cells and the medium to new wells. The three groups differed markedly in their capacity to synthesize IgE. The atopic dermatitis group demonstrated high spontaneous IgE synthesis (median 11.8 ng/ml), which was doubled (24.3 ng/ml, p < 0.05) by stimulation by IL-4. The two other groups had low spontaneous synthesis (0.7 and 0.3 ng/ml) but this increased (1.7 and 0.7 ng/ml, p<0.01) upon IL-4 stimulation. The spontaneous production of IFN-gamma in the cultures did not differ between the groups, but upon stimulation with phorbol myristate acetate, the atopic dermatitis group demonstrated significantly lower IFN-gamma levels compared to the two other groups. The IL-4 production in the cultures were generally below the detection limit (100 pg/ml), and whereas plasma levels of 1-2 ng/ml of soluble IL-4 receptor could be detected in all donors, no differences could be detected between the groups. These data suggest that reduced ability in atopic dermatitis of mounting an IFN-gamma response may account for the high levels of plasma IgE and IgE synthesis found in these patients.