Procaterol potentiates the anti-inflammatory activity of budesonide on eosinophil adhesion to lung fibroblasts.

BACKGROUND: The interaction between leukocytes and various parenchymal cells is the first step of inflammation. Therefore, the adhesion of eosinophils to lung fibroblasts is thought to be a crucial step in the inflammatory process of asthma. Procaterol, a beta(2)-selective full agonist, is currently prescribed for patients with asthma. In addition to its potent bronchodilatory action, the agonist has been reported to have anti-inflammatory actions. In this study, to examine whether procaterol can potentiate the anti-inflammatory action of glucocorticoids, the effect of procaterol on eosinophil adhesion to normal human lung fibroblasts (NHLF) was assessed in the presence and absence of budesonide, one of the most potent glucocorticoids. METHODS: Following pretreatment of NHLF with tumor necrosis factor-alpha (TNF-alpha) in the presence of various concentrations of procaterol and/or budesonide, the eotaxin-stimulated eosinophil adhesion was determined using the peroxidase activity of eosinophils. To investigate the mechanism of the inhibitory action of procaterol, TNF-alpha-induced expression of adhesion molecules, ICAM-1 and VCAM-1, in NHLF was also evaluated. RESULTS: Pretreatment with procaterol inhibited the adhesion of eosinophils to NHLF in a concentration-dependent manner, and shifted the concentration-response curve of budesonide to the left. Both procaterol and budesonide resulted in concentration-dependent inhibition of expression of ICAM-1 and VCAM-1 in NHLF, and an additive inhibitory effect was found when the agents were combined. CONCLUSIONS: Given the results of this study which indicated that procaterol exerted an additive action on the anti-inflammatory effect of budesonide, procaterol and glucocorticoids may provide better control for asthma when used together than when used separately.

Adrenal influences on the inhibitory effects of procaterol, a selective Beta-two-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in Guinea pigs.

While the guinea pig has been the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, it has been shown that antigen-induced bronchoconstriction in guinea pigs is attenuated by epinephrine released from the adrenal gland. In order to investigate the possible influence of the adrenal gland on the effects of antiexudative and bronchodilative drugs on antigen-induced airway responses, we examined the inhibitory effects of procaterol, a selective beta(2)-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in adrenalectomized guinea pigs and compared them with the drug's effects in sham-operated animals. Guinea pigs sensitized passively with anti-ovalbumin (OA) guinea-pig serum were adrenalectomized or sham-operated under urethane anesthesia and examined 30 min after surgery in the following experiments. (1) Animals were intravenously administered Evans blue dye to quantify airway plasma exudation, and then OA was inhaled for 10 min while measuring pulmonary inflation pressure, a parameter of bronchoconstriction. Procaterol (1, 3, 10, or 30 microg/kg) or saline (control) was administered into the airways 10 min prior to OA inhalation. The amount of extravasated Evans blue dye in the airways was calculated. (2) Venous blood samples were collected during OA or saline inhalation and plasma catecholamine levels were compared. In control animals, OA-induced increases in both the amount of Evans blue dye and in pulmonary inflation pressure were markedly greater in adrenalectomized animals than in sham-operated animals. Procaterol dose-dependently inhibited OA-induced airway microvascular leakage and bronchoconstriction, and its effects were more potent in adrenalectomized animals (significant at 1 microg/kg and higher) than in sham-operated animals (significant at 10 microg/kg and higher). Although the plasma concentration of epinephrine during OA inhalation was approximately 3 times higher than that during saline inhalation in sham-operated animals, no difference was seen in adrenalectomized animals. In conclusion, while procaterol essentially possesses pronounced inhibitory effects on antigen-induced airway microvascular leakage and bronchoconstriction in guinea pigs, the effects are considerably masked by epinephrine released from the adrenal gland.