Interactions between histamine and prostanoids in IgE-dependent, late cutaneous reactions in man

The contribution of histamine and cyclooxygenase metabolites of arachidonic acid to the wheal-and-flare reaction (WFR) (0 to 30 minutes) and the late cutaneous reaction (LCR) (1 to 24 hours) evoked by intradermal injection of antihuman IgE was appreciated in a comprehensive study of human volunteers treated with H1 and H2 antihistamines, cyclooxygenase inhibitors, as well as the combination of both types of drugs. The findings reinforce the concept that histamine is the major, but not exclusive, mediator of the WFR. In contrast, histamine accounted for but a limited portion of the LCR, but 48 hours of pretreatment with three different cyclooxygenase inhibitors, acetylsalicylic acid, indomethacin, or diclofenac sodium, had but a minor influence on the WFR, whereas all drugs produced a distinct overall inhibition of the LCR. However, for indomethacin, the inhibition was preceded by a potentiation (at 1 to 2 hours), which was abolished by antihistamines, suggesting increased histamine release from skin mast cells after cyclooxygenase inhibition. Furthermore, there was synergism between indomethacin and antihistamines during the LCR, and the combination of diclofenac sodium with antihistamines produced additive inhibition. It is proposed that cyclooxygenase products, such as prostaglandins and thromboxanes, contribute to IgE-dependent skin reactions, both as modulators of mediator release and as vasoactive mediators.