Allergen-Induced Mucosal Exudation of Plasma into Rat Ileum and Its Inhibition by Budesonide

Abstract

Exudation of plasma across the airway mucosa is a specific defence/inflammatory response finely regulated by mediators and (in rodents) a capsaicin-sensitive innervation. This study examines plasma exudation responses to endointestinal challenges and effects of a glucocorticoid. The ileum of anesthetized rats was catheterized and ligated at two points 10 cm apart for mucosal challenge (0.5 ml) and repeated lavages (5 ml). Lavage fluid levels of the plasma tracer 125I-albumin, previously injected intravenously, showed a stable, low base line greater than 2 h. Challenge with mediators (10(-5) M bradykinin, 10(-5)-10(-3) M serotonin, 10(-6)-10(-4) M histamine, 2.10(-9)-2.10(-7) M leukotriene D4 (LTD4), or 10(-5)-10(-3) M capsaicin did not increase luminal radioactivity. However, allergen (10(-6) M ovalbumin, in previously sensitized animals) produced prompt mucosal exudation of 125I-albumin, peaking within 30 min (p less than 0.001) and returning to base line within 90 min. Separate experiments suggested that absorption was not increased during the mucosal exudation. The glucocorticoid budesonide (10-1000 micrograms/kg given by gavage 24 h before challenge) dose-dependently inhibited the allergen-induced exudation (p less than 0.01). The route of administration and the antiexudative versus the systemic potency (reduced thymus weight) suggest the possibility of a topical action of budesonide. We conclude that endointestinal allergen challenge produces reversible and glucocorticoid-inhibitable exudation of plasma across the mucosa. It appears less likely that bradykinin, serotonin, histamine, LTD4, or a capsaicin-sensitive innervation is involved in producing this exudative effect.