Inhibition of IgE-mediated histamine release from human leukocytes by a new xanthine derivative, D 4026

Abstract

Pretreatment of human leukocytes with the new xanthine compound, 3,7-dihydro-1,8-dimethyl-3-phenyl-1H-purine-2,6-dione (D 4026), induced a dose-dependent and statistically significant inhibition of immunoglobulin E-mediated histamine release in the concentration interval 0.1-1000 microM. Histamine release elicited with suboptimum amounts of the triggering agent (anti-IgE or antigen) was inhibited to a greater extent than a release initiated with optimum amounts. At a concentration of 10 microM, D 4026 had at least the same inhibitory effect as 100 microM theophylline. When leukocytes were incubated simultaneously with D 4026 and a histamine H-2 receptor-stimulating drug (histamine or clonidine), the two drugs combined induced an inhibition significantly greater than the sum of their individual inhibitory effects. Only pure additive inhibitory effects were, however, obtained during simultaneous treatment of leukocytes with theophylline and histamine.

The Glucocorticosteroid, Budesonide, Partially Blocks Histamine Release from Human Lung Tissue in Vitro

“…Moreover, diluted reagin-rich serum or the diluent or budesonide (at a final concentration as indicated below) / vehicle, was added. Incubation was performed in a total volume of 1 ml of 37°C overnight, the fragments were washed, and finally resuspended i HEPES-ACM buffer (21).…”

Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

“…The work of Radermecker (29) and pilot experiments of our own showed that there was no apparent difference in the release induced by allergen or by anti-IgE of blood tested immediately or after storage in a refrigerator for 24 h. The day after blood harvest, the leukocytes were separated by sedimentation in a mixture of dextran-EDTA and glucose and washed twice in HEPES-A buffer, as described previously (6,26). Because of the transportation times required, the blood was kept at approximately 2^°C one day before the test was performed.…”

“…Because of the transportation times required, the blood was kept at approximately 2^°C one day before the test was performed. The work of Radermecker (29) and pilot experiments of our own showed that there was no apparent difference in the release induced by allergen or by anti-IgE of blood tested immediately or after storage in a refrigerator for 24 h. The day after blood harvest, the leukocytes were separated by sedimentation in a mixture of dextran-EDTA and glucose and washed twice in HEPES-A buffer, as described previously (6,26). Following tbe reconstitution of leukocytes in the appropriate amounts of HEPES-ACM (HEPES-A buffer supplemented witb Ca2+ and Mg2+) (6), challenge was performed with allergen or anti-IgE in an appropriate dilution or vehicle.…”

“…The release reaction was stopped after 40 min at 37°C by immersing the tubes in ice. Histamine was extracted and assayed spectrophototluorometrically as described elsewhere (11,26). Histamine release was expressed as a percentage of the total cellular histamine content after correction for spontaneous release.…”

“…Histamine release was expressed as a percentage of the total cellular histamine content after correction for spontaneous release. The antigen preparations used were of the same batch as that used for bronchial challenge experiments; anti-IgE was prepared as described elsewbere (26).…”