Allergen-induced Biphasic Plasma Exudation Responses in Guinea Pig Large Airways

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Abstract
In this study involving sensitized guinea pigs (anesthetized intramuscularly with a 3:2 mixture of ketamine+xylazine, 1 ml/kg), we applied allergen (ovalbumin) selectively to the tracheobronchial mucosa (sparing the nasal passages and the terminal airways) and examined the occurrence of immediate and late-phase inflammatory exudation of plasma and plasma-derived mediators (bradykinins) into the airway lumen. The experiments were terminated 10 to 480 min after challenge. A selective lavage that sampled the surface liquids of the extrapulmonary bronchi and the lower trachea was performed. The amount of plasma (microliter) was determined by analysis of a plasma tracer, [125I]albumin, in lavage fluid and blood (plasma) samples. Ovalbumin, 3 to 12 pmol, and histamine, 5 and 10 nmol, produced a dose-dependent immediate exudation response (p < 0.001). The effects were nonneurogenic because they were not affected by topical lidocaine given in a dose (3 nmol) that prevented the exudative effect of capsaicin. The 6- and 12-pmol doses of ovalbumin (but not 3 pmol) produced a significant late-phase exudative response at 5 h (p < 0.001), and both the immediate and late phases were associated with increased (p < 0.01 to p < 0.001) levels of bradykinin in the lavage fluids. Histamine, even in doses that produced a greater early response than the allergen, did not produce a late-phase response. A single topical dose of an antiasthma steroid (budesonide, 12 mumol/kg) administered just before ovalbumin (6 pmol) had little effect on the immediate response but inhibited the late-phase response (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)