An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E-mediated asthma in rhesus monkeys |
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Authors: | Roy Patterson M.D. Jacob J. Pruzansky Ph.D. Kathleen E. Harris B.S. |
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Affiliation: | From the Section of Allergy-Immunology, Department of Medicine, Northwestern University Medical School, Chicago, Ill., USA |
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Abstract: | An inhibitor of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism, BW755C, was evaluated with the rhesus monkey model of IgE-mediated asthma. BW755C was found to release histamine from human and rhesus peripheral blood leukocytes and rhesus bronchial lavage cells. BW755C did not induce a rhesus airway response but inhibited antigen-induced airway changes in pulmonary resistance and dynamic compliance. The results demonstrated that a lipoxygenase and cyclooxygenase inhibitor that is a histamine releaser may inhibit some pulmonary function abnormalities of an IgE-mediated response and suggested that histamine has a minor role as a stimulator of airway reaction in this model. This was supported by studies showing failure of the histamine H1 blocker pyrilamine maleate to inhibit the antigen-induced airway response. Although BW755C has been shown to be a lipoxygenase and cyclooxygenase inhibitor, it is not established that the inhibiting action of this agent on an antigen-induced airway response is due to an effect on arachidonate metabolism in the lung. |
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Keywords: | Reprint requests to: Roy Patterson M.D. Northwestern University Medical School Department of Medicine 303 East Chicago Ave. Chicago IL 60611. |
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