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 asthma due to aerosol challenge with ascaris has been developed to the status of an analytic system for agents capable of inhibiting the antigen-induced airway response. Two antigen-challenge systems have been 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 of these types of response were inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA). This action may be through the inhibition of the lipoxygenase 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 first agent, other than beta agonists or cromolyn, that we have been able to demonstrate as clearly having an inhibitory action on the rhesus monkey model of asthma.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release; D007073:Immunoglobulin E / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D012882:Skin Tests
D000941:Antigens; D005231:Fatty Acids, Unsaturated; D015117:5,8,11,14-Eicosatetraynoic Acid; D007073:Immunoglobulin E