Temporal relationships between leukocytes, IL-5 and IL-8 in guinea pig lungs, plasma cortisol and airway function after antigen challenge

Objective and Design: The aim was to determine the time courses for the cha nges in airway function, airway reactivity, influx of inflammatory cells an d levels of the proinflammatory cytokines, interleukin (IL)-5 and IL-8 in b ronchoalveolar lavage fluid (BALF), and the plasma levels of cortisol and A CTH after antigen challenge to determine whether a temporal link could be e stablished between these events. Methods: Airway function was measured as specific airway conductance (sG(sw )) in conscious ovalbumin (OvA)-sensitized guinea pigs using whole body ple thysmography at intervals after an inhalation challenge with ovalbumin (0.5 % for 10 min). Airway responses to the inhaled spasmogen, U46619 (30 ng/ml, 60s), were measured at 3, 6 and 24h after challenge, In separate animals, bronchoalveolar lavage fluid (BALF) was obtained after anaesthetic overdose either before challenge or at 1, 3, 6, 12, or 24h after OvA challenge. Tot al and differential cell counts of eosinophils and neutrophils were perform ed on BALF and levels of IL-5 and IL-8 determined by scintillation proximit y assays and ELISA, respectively. Plasma cortisol and ACTH levels were dete rmined by RIA kits in blood removed by cardiac puncture at intervals after challenge. Results: An early phase bronchoconstriction occurred which resolved by 3 h and was followed by a late phase between 17 and 24h, Airway hyperresponsive ness to inhaled U46619, was evident at 3, 6 and 24h after antigen challenge . Increased IL-5([BALF]) Was observed by 60 min post challenge implicating a preformed storage site. In contrast, IL-8([BALF]) was not raised until 3 h post challenge. There was a significant infiltration of neutrophils and e osinophils by 3 and 6 h, respectively. IL-5([BALF]) further increased up to 24 h, during the appearance of the late phase of bronchoconstriction and w hilst eosinophilia was maximal. Plasma cortisol levels were increased 1 and 3 hours after antigen challenge, thereafter returning to baseline levels. Conclusions: The hyperresponsiveness appears to be dissociated from the app earance of eosinophils in lavage fluid. The early appearance of IL-5, howev er, could be a trigger for the migration of eosinophils and development of hyperresponsiveness. The increased plasma cortisol levels occurring after a ntigen challenge were presumably due to the stress involved and these would be expected to exert an endogenous anti-inflammatory effect.