TY - JOUR

T1 - Biomolecular regulation of the ige immune response

T2 - ii in vitro ige synthesis and spontaneous production of cytokines

AU - Poulsen, L. K.

AU - Reimert, C. M.

AU - Bindslev-Jensen, C.

AU - Hansen, M. B.

AU - Bendtzen, K.

PY - 1995

Y1 - 1995

N2 - 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 o f donors: (1) patients with atopic dermatitis and high levels o f scrum 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 11-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 o f IFN-y in the cultures did not differ between the groups, but upon stimulation with phorbol myristate acetate, the atopic dermatitis group demonstrated significantly lower IFN-y 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/nil 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-y response may account for the high levels of plasma IgE and IgE synthesis found in these patients.

AB - 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 o f donors: (1) patients with atopic dermatitis and high levels o f scrum 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 11-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 o f IFN-y in the cultures did not differ between the groups, but upon stimulation with phorbol myristate acetate, the atopic dermatitis group demonstrated significantly lower IFN-y 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/nil 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-y response may account for the high levels of plasma IgE and IgE synthesis found in these patients.

KW - Allergy

KW - Atopic dermatitis

KW - B lymphocytes

KW - Ige

KW - Interferon-gamma

KW - Interleukin-4

KW - Soluble il-4 receptor

UR - http://www.scopus.com/inward/record.url?scp=0028851381&partnerID=8YFLogxK

U2 - 10.1159/000236890

DO - 10.1159/000236890

M3 - Journal article

C2 - 7812167

AN - SCOPUS:0028851381

VL - 106

SP - 55

EP - 61

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

SN - 1018-2438

IS - 1

ER -