Enhancement of basophil histamine release by interleukin-3: reduced effect in atopic subjects

The inducing and enhancing effects of interleukin-3 (IL-3) on basophil histamine release in patients with respiratory allergy (n = 28) and in normal subjects (n = 22) were compared. Leukocyte suspensions, prepared by dextran sedimentation, were stimulated with anti-IgE (1/5000), N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM), and IL-3 (0.1-10 ng/ml), and histamine concentration was measured by an automated fluorometric method. A trend toward higher histamine release after challenge with anti-IgE, FMLP, and IL-3 was found in atopic subjects. Preincubation of basophils with IL-3 resulted in a dose-dependent increase of anti-IgE- and FMLP-induced histamine release, with a more marked effect in nonatopic than in atopic subjects. Mean net enhancement of anti-IgE-induced histamine release by 10 ng/ml IL-3 was 2.5 +/- 5% in atopic subjects and 29.6 +/- 4.2% in nonatopic subjects (P < 0.001). The enhancement of FMLP-induced histamine release by IL-3 was 10.3 +/- 3.9% in atopic patients and 29 +/- 2.4% in nonatopic subjects (P < 0.01). In atopic subjects, a negative correlation was found between anti-IgE- or FMLP-induced histamine release and net enhancement by IL-3 (r = -0.45, P < 0.02; r = -0.48, P < 0.01, respectively). The results of this study indicate that in atopic subjects IgE-mediated histamine release can scarcely be enhanced by a basophil response modifier such as IL-3. It is conceivable that the frequent basophil stimulation in atopic patients leads to a reduced sensitivity to the enhancing effect of IL-3.