A selective inhibitor of thromboxane biosynthesis enhances immediate and inhibits late cutaneous allergic reactions in man

Abstract

Thromboxanes may be involved in late cutaneous reactions (LCRs). A new selective inhibitor of thromboxane biosynthesis was studied for its effect on immediate skin test reactions (WFRs) and LCRs in nine adult nonatopic volunteers (open study) and eight adult atopic patients (double-blind study vs. placebo). WFRs and LCRs were elicited by intradermal injections of 25 μg of compound 48 80 and 200 IU of rabbit anti-human IgE antibodies, and the patients' receiving injections of 0.32, 1.6, 8, 40, and 200 IU of anti-IgE antibodies. Dazoxiben (100 mg orally three times once every 4 hr) increased the diameter of wheals (p < 0.005 in volunteers; p < 0.05 in six patients receiving no additional drug treatment), favored their dispersion (lymphangitis/pseudopodia), and caused systemic reactions (headache, chills) in at least two out of eight patients. Edema formation during LCRs was markedly depressed in 13 out of 16 persons. Flare diameter and erythemata during LCRs were not altered. These data suggest a role of thromboxanes and their natural antagonists (e.g., prostacyclin) in the regulation of allergic inflammatory processes.