INHIBITION OF IMMUNOGLOBULIN-E-MEDIATED, ANTIGEN-INDUCED MONKEY ASTHMA AND SKIN REACTIONS BY 5,8,11,14-EICOSATETRAYNOIC ACID

The immediate-type, IgE-mediated rhesus monkey model of [human] asthma due to aerosol challenge with Ascaris was developed to the status of an analytic system for agents capable of inhibiting the antigen-induced airway response. Two antigen-challenge systems were developed. The standard Ascaris challenge uses a dose of antigen that will induce an airway response in all reactive animals. In the threshold antigen-challenge system, the threshold dose of antigen that will induce an airway response is determined and is relatively constant for the individual animal. Both types of response were inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA). This action may be through the inhibition of the lipoxgenase and cyclooxygenase metabolic pathways of arachidonic acid and possibly through inhibition of production of slow-reacting substance. ETYA also inhibits cutaneous immediate-type reactivity to Ascaris antigen in a dose-response relationship. This may be the result of inhibition of mast cell histamine release or the inhibition of production of other vasoactive mediators. An alternative explanation for the action of ETYA in the airway and skin responses is that ETYA may act as an end-organ antagonist to released bioactive mediators. ETYA is the 1st agent, other than .beta.-agonists or cromolyn, than clearly have an inhibitors action on the rhesus monkey model of asthma.