title: Increased sensitivity to toluene diisocyanate (TDI) in airways previously exposed to low doses of TDI.
abstract: 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)
authors.affiliation: Department of Pharmacology 1, ASTRA DRACO, Lund, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Erjefält
authors.forename: C G
authors.initials: CG
authors.lastname: Persson
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D019819:Budesonide; D006168:Guinea Pigs; D007249:Inflammation; D007442:Intubation, Intratracheal; D008297:Male; D011282:Pregnenediones / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000188:drug therapy; D013806:Theophylline / Q000627:therapeutic use; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000633:toxicity*; D014970:Xanthines / Q000627:therapeutic use
chemical_list: D011282:Pregnenediones; D014970:Xanthines; D014051:Toluene 2,4-Diisocyanate; D019819:Budesonide; D013806:Theophylline; C034347:enprofylline