The effect of terfenadine on the immediate and late-phase reactions mediated by immunoglobulin E.
Basophils in mononuclear cell populations were challenged with allergens, anti-immunoglobulin E (anti-IgE), C5a or formyl-methyl-leucyl-phenylalanine (FMLP), with or without a short pre-incubation with interleukin-3 (IL-3), in the presence of increasing concentrations of terfenadine. At doses of 0.1-1 micrograms/ml, terfenadine inhibits histamine release and generation of the sulfidoleukotrienes, leukotriene C4, D4 and E4 in basophils challenged with an IgE-dependent trigger. At concentrations above 10 micrograms/ml, however, terfenadine induces the histamine release but abolishes the formation of leukotrienes, and this may be due to a cytotoxic effect. In eosinophils, by contrast, terfenadine appears to inhibit the production of leukotrienes by eosinophils, triggered by FMLP only at concentrations above 10 micrograms/ml (which are toxic to basophils at least). In a double-blind, placebo-controlled study, 15 allergic patients were given skin challenges with specific allergen and with histamine, before and at 3 days, 2 and 4 weeks after treatment with terfenadine (120 mg/day for 3 days). The skin reactions were evaluated visually and followed kinetically by thermography. Terfenadine caused a significant decrease in both the immediate and late-phase reactions. Late-phase reactions to histamine were shown with thermography in some of the patients tested.
de Weck
A L
AL
Institute of Clinical Immunology, Bern, Switzerland.
Derer
T
T
Bischoff
S C
SC
Takafuji
S
S
D000284:Administration, Oral; D000485:Allergens; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects; D002176:Candida albicans / Q000276:immunology; D015936:Complement C5a / Q000494:pharmacology; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007377:Interleukin-3 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D006109:Poaceae / Q000276:immunology; D012882:Skin Tests; D016593:Terfenadine / Q000008:administration & dosage / Q000494:pharmacology*; D013817:Thermography / Q000379:methods; D013997:Time Factors
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D007377:Interleukin-3; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016593:Terfenadine; D015936:Complement C5a; D006632:Histamine