title: Delayed-type asthmatic response induced by repeated intratracheal exposure to toluene-2,4-diisocyanate in guinea pigs.
abstract: BACKGROUND
  A toluene-2,4-diisocyanate (TDI)-induced asthma model, in which delayed-type hypersensitivity-like asthmatic airway obstruction is elicited restrictively in the lung, has never been developed.
  
  
  METHODS
  Guinea pigs were percutaneously sensitized with TDI. For the challenges, once every 2 weeks for a total of 5 times, TDI mists were delivered directly to the lung through an oral cannula, with its tip being positioned in the opening of the trachea. Time-course changes in specific airway resistance (sRaw) were measured by double-flow plethysmography. Basic mechanisms underlying TDI-induced asthma were analyzed.
  
  
  RESULTS
  After the 2nd-5th challenges, induction of both an early increase in sRaw that peaked at 10 min and a delayed-type sRaw elevation that peaked at 22 h were observed. Interestingly, in the sensitized/challenged animals, baseline sRaw was elevated by repeated challenge as compared to that seen for non-sensitized animals. Intratracheal administration of a bronchodilator, salbutamol, strongly suppressed the early asthmatic response (EAR) but not the delayed-type asthmatic response (DAR). During DAR, both albumin leakage and fucose secretion into the bronchoalveolar lavage fluid were increased. The cysteinyl leukotriene antagonist pranlukast failed to inhibit either EAR or DAR while the corticosteroid dexamethasone significantly suppressed DAR, without significantly affecting EAR.
  
  
  CONCLUSIONS
  Effective delivery of TDI to the lung may induce reproducible DAR in sensitized guinea pigs with chronicity that is reflected by an increase in the sRaw baseline. DAR is not mediated by constriction of airway smooth muscles and is probably due to the concurrent presence of mucosal edema and mucus hypersecretion in the airways.
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
authors.forename: Kanami
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinjo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Kenji
authors.initials: K
authors.lastname: Imoto
authors.forename: Akihide
authors.initials: A
authors.lastname: Koda
authors.forename: Shigekatsu
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000403:Airway Resistance; D000418:Albumins / Q000378:metabolism; D000420:Albuterol / Q000494:pharmacology; D000485:Allergens / Q000276:immunology / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D002867:Chromones / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005643:Fucose / Q000378:metabolism; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000633:toxicity*; D014132:Trachea
chemical_list: D000418:Albumins; D000485:Allergens; D002867:Chromones; D007074:Immunoglobulin G; D014051:Toluene 2,4-Diisocyanate; D005643:Fucose; D007073:Immunoglobulin E; D003907:Dexamethasone; D000420:Albuterol; C047681:pranlukast