The program has the following goals and objectives. 1. To maintain a colony of 3 groups of rhesus monkeys including normal animals, animals with IgE mediated cutaneous and airway reactivity to ascaris antigen or animals with IgE positive skin reactivity but negative airway reactivity. Because the antigen airway reactors have hyperreative airways this group of allergic rhesus monkeys may closely simulate human IgE mediated asthma. 2. To establish quantitative dose-response reactions to antigen and carbocholine in antigen reactive monkeys and carbocholine reactivity in normal monkeys. The carbocholine reactivity will be an index of the degree of hyperreactivity of the airway. 3. To determine qualitative and quantitative responses to potentially important agonists of airway reactions in selected asthmatics and controls monkeys. These agonists will include leukotriene D4 (LTD4), platelet activating factor (PAF) and histamine releasing agent (HRA) in selected asthmatic and control monkeys for evaluation of qualitative and quantitative individual animal responses. 4. To study receptor antagonists against LTD4 and PAF as inhibiting agents for these agonists and for antigen induced asthma. A lipoxygenase inhibitor will be studied to determine if antigen induced asthma is diminished by pretreating with this agent. The airway response to HRA will be evaluated by using antagonists against H, LTD4 and PAF. 5. To define the pattern of bioactive mediators released into bronchoalveolar lavage (BAL) fluid after antigen challenge and challenge with these mediators. 6. To develop a monkey model of toluene diisocyanate (TDI) asthma based on our human clinical experience in man and our experience with a canine model of TDI asthma.
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