Airway Response to Leukotriene D₄ in Rhesus Monkeys

Abstract

We studied the effect of leukotriene D₄ (LTD₄) given by aerosol challenge on asthmatic and normal monkeys. The response to LTD₄ occurred within 2 min., was prolonged at higher concentrations, was reversed by epinephrine, and more closely resembled an antigen response than a histamine response. Since LTD₄ concentrations of 30–100 μg/ml produced a response similar to 2–20 mg/ml of histamine, the LTD₄ was 300–900 times as potent as histamine on a molar basis. Thus, LTD₄, which appears to reproduce an antigen-induced response in rhesus monkeys, may be a mediator of allergic asthma in these animals.

Plasma Levels of Leukotrienes C₄ and D₄ during Wheezing Attack in Asthmatic Patients

“…Dahlen et al [7] detected LTC4, LTD4, and LTE4 after allergen challenge of lung tissue from asthmatics. Inhalation of LTC4 and LTD4 to monkeys and human subjects suggested a contributory role of leukotrienes during asthmatic attack [3,16]. However, there are few re ports about the release in vivo of LTs from asthmatic patients.…”

Rhesus Monkey Airway Responses to Substance P

“…This model has been used for characterization of rhesus bronchial responses to LTD4 [3], PAF [4], and other bioactive mediators.…”

“…We now report that SP produces an airway re sponse analogous in quality to that resulting from an tigen, LTD4, PAF or histamine [2][3][4]17], The concen tration of SP producing a response is analogous to the concentration of histamine that produces an airway response in this species [ 17], The concentration of SP producing an airway re sponse was similar in rhesus monkeys with positive skin reactivity to AA antigen whether or not the ani mal had airway reactivity to AA. Previous studies of these populations of monkeys have shown that the animals with IgE antibody against AA, shown by cu taneous reactivity to AA, which also had an airway response to AA, had airway hyperactivity as demon strated by carbachol responsiveness.…”

“…These criteria represent means!standard deviation over control values. A minimal positive response is one in which three of five parameters meet the above criteria (3). Extensive study of this model has shown that the number of abnormal responses meeting the criteria of abnormality reflects a more significant response than the degree of response of any single parameters 112,13], l Cutaneous Reactivity Monkeys were anesthetized and received 5 ml of 0.5% Evans' blue dye intravenously.…”

“…The rhesus monkey model of asthma is an IgE-me diated, acute airway response to Ascaris antigen (AA) [1] which occurs in animals with hyperactive airways demonstrated by increased airway reactivity to carbocholine [2], In studies evaluating the mediator theory of asthma, various bioactive mediators including leukotriene D4 (LTD4) [3] and platelet-activating factor (PAF) [4] have been characterized in these animals. Most recently, the effect of a lipoxygenase antago nist has been reported using the rhesus model of asth ma [5].…”