Inhibition of basophil histamine release by methotrexate.
Basophil leukocytes in whole blood from 4 healthy donors, 4 atopic patients, and 10 female patients operated for breast-cancer were preincubated from 1 to 20 hrs alone or in the presence of methotrexate (MTX) or MTX and folinic acid. After preincubation, the basophil leukocytes were challenged with anti-IgE, allergens or the calcium ionophore A23187 in the presence of 25 ng/ml TPA (12-o-tetradecanoyl-phorbol-13-acetate). A 9-hr preincubation with MTX produced significant inhibition of histamine release (greater than 20%) at 500-50 micrograms/ml. This effect increased up to 20 hrs of incubation, displaying maximal activity (100% inhibition) at 500 micrograms/ml, but even submicrogram concentrations (0.5 microgram/ml) produced significant inhibition. The addition of folinic acid did not alter the inhibition. It is concluded that MTX with or without the addition of folinic acid is a potent inhibitor of histamine release induced by anti-IgE, allergens, and A23187 combined with TPA. Like glucocorticoids the mechanism of action of MTX may be linked to arachidonate metabolism, but may interrupt earlier steps in prostaglandin synthesis.
Nolte
H
H
Dept. of Oncology ONA, Finsen Institute, Copenhagen, Denmark.
Stahl Skov
P
P
D000328:Adult; D000368:Aged; D001491:Basophils / Q000187:drug effects / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D066298:In Vitro Techniques; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged
D008727:Methotrexate