Chronological relationships between mediator release and changes in airway dynamics during an ascaris response in sensitive cynomolgus monkeys

Recently identified Ascaris suum sensitive cynomolgus monkeys were further characterized to determine if a chronologic relationship existed between mediator release and onset of bronchoconstriction. In these anesthetized Ascaris-sensitive monkeys, aerosol antigen challenge of each animal produced rapid and severe bronchoconstriction, as determined by decreases in dynamic lung compliance (-80.2 +/- 4.1%) and airway conductance (-64.5 +/- 13.8%). Maximum changes were achieved within 5 min following exposure and remained substantially altered throughout the 30 min observation period. However, changes in pulmonary function related to duration of onset and maximum change seemed to have some correlation with each animals' sensitivity to the antigen. Comparison of pre- and post-challenge blood gas profiles, showed a progressive formation of respiratory acidosis through decreases in arterial blood pH, partial pressure of O2 (pO2), O2 saturation (sO2) and an increase in partial pressure of CO2 (pCO2). When arterial blood plasma was assayed by RIA for mediators of anaphylaxis, large increases in 5-hydroxyeicostetraenoi acid (5-HETE), leukotriene B4 (LTB4) and histamine were observed. No amount of prostaglandin F2-alpha (PGF2 alpha) or thromboxane A2 were detected. Two of the three monkeys also produced detectable amounts of leukotriene C4 (LTC4). Therefore, in Ascaris-sensitive monkeys, histamine is the predominate mediator released and is probably responsible for at least the early part (5-10 min) of the observed bronchoconstriction. However, mediators from the lipoxygenase pathway may also be playing a role in the antigen-induced bronchoconstriction, especially beyond the 10 min period following anaphylaxis.