pulmicort and enprofylline

Repeated airway exposures to toluene diisocyanate (TDI) may cause sensitization and asthma. This study has examined the acute inflammatory response to TDI in guinea-pig tracheobronchial airways, the development of increased sensitivity to TDI and the effects of xanthines and a glucocorticoid on these responses to TDI. A restricted surface area of the tracheobronchial mucosa of Ketalar-Xylazin anaesthetized guinea-pigs was exposed to TDI, dissolved in olive oil, by means of 1 min infusions through an oral catheter. The TDI-induced inflammatory process was quantified by determination of airway luminal entry of plasma. Already 3 nl (approximately 20 pmol) of TDI produced a significant and sustained exudation response (P less than 0.001 to P less than 0.01, 5 and 17 hr after exposure). Pretreatment with intravenous enprofylline (25 mumol/kg) intraperitoneally or 26 mumol/kg by tracheal superfusion) was without effect. Two repeated exposures to TDI 3 nl (on days 1 and 8) made the animals hyperresponsive to TDI so that on day 15 a previously subthreshold dose of TDI (0.3 nl) produced significant exudation both at 5 and 17 hr after exposure (P less than 0.001 to P less than 0.01). Similarly, two repeated dermal exposures to a large dose of TDI (20 microliters) lowered the threshold for tracheal provocation with TDI. Budesonide (2.6 mumol/kg orally) given daily during the topical airway 'sensitization' regimen (days 1-14) significantly reduced the response to the subsequent 0.3 nl challenge dose of TDI (P less than 0.05). The effects of daily treatments with either theophylline (100 mumol/kg) or enprofylline (50 mumol/kg) were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Cutaneous; Administration, Topical; Animals; Budesonide; Guinea Pigs; Inflammation; Intubation, Intratracheal; Male; Pregnenediones; Respiratory Hypersensitivity; Theophylline; Toluene 2,4-Diisocyanate; Xanthines

In vitro incubation of IgE-sensitized guinea-pig tracheal rings with 10(-7) M budesonide for 24 h significantly shifted the concentration-response curve to antigen by 5-fold to the right. Smooth muscle characteristics such as baseline tone, muscarinic contraction or relaxation to beta 2-receptor agonists and xanthines were not or only marginally affected by this exposure of airway tissue to a glucocorticoid drug. It is concluded that budesonide reduced anaphylactic IgE-driven release of contractile mediators.

Topics: Airway Resistance; Animals; Budesonide; Carbachol; Drug Interactions; Glucocorticoids; Guinea Pigs; Immunoglobulin E; In Vitro Techniques; Ovalbumin; Pregnenediones; Terbutaline; Trachea; Xanthines

An investigation was carried out to determine whether the sensitivity of rat tracheal smooth muscle to contractile and relaxant drugs was affected by three weeks' treatment with subcutaneous budesonide before death. Budesonide treatment was associated with a lower thymus weight and a smaller gain in body weight than in control animals. There was, however, no difference in the carbachol concentration-response curves or maximum responses to carbachol of tracheal smooth muscle from control and budesonide treated rats. Isometric and isotonic recordings agreed in these respects. Glucocorticoid treatment did not increase the sensitivity of tracheal smooth muscle to the relaxant drugs terbutaline and enprofylline; if anything there was a tendency for terbutaline and enprofylline to be less potent after budesonide treatment. The data suggest that in vivo effects of glucocorticoids on airway responsiveness to bronchodilating and bronchoconstricting drugs are unlikely to be due to a direct effect on bronchial smooth muscle.

Topics: Animals; Body Weight; Budesonide; Carbachol; Culture Techniques; Glucocorticoids; Male; Muscle Contraction; Muscle, Smooth; Pregnenediones; Rats; Rats, Inbred Strains; Terbutaline; Thymus Gland; Trachea; Xanthines