INCREASED SENSITIVITY TO TOLUENE DIISOCYANATE (TDI) IN AIRWAYS PREVIOUSLY EXPOSED TO LOW-DOSES OF TDI
INCREASED SENSITIVITY TO TOLUENE DIISOCYANATE (TDI) IN AIRWAYS PREVIOUSLY EXPOSED TO LOW-DOSES OF TDI
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DOI：
10.1111/j.1365-2222.1992.tb02831.x
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发表时间：
1992-09-01
影响因子：
6.1
通讯作者：
PERSSON, CGA
中科院分区：
文献类型：
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作者：
ERJEFALT, I;PERSSON, CGA
反复呼吸道接触甲苯二异氰酸酯(TDI)可能会导致过敏和哮喘。本研究观察了豚鼠气管、支气管对TDI的急性炎症反应，对TDI敏感性增加的发展，以及黄嘌呤和糖皮质激素对这些反应的影响。在Ketalar-Xylazin麻醉的豚鼠气管、支气管粘膜上暴露于TDI，溶解于橄榄油中，经口腔导管注入1min。TDI诱导的炎症过程通过测定血浆的气道腔进入来量化。已经有3nL(约20pmol)的甲苯二异氰酸酯产生了显著和持续的渗出反应(P<；0.001对P<；0.01、5和17小时)。静脉注射恩普罗林(25mumol/kg)可降低5h的急性反应(P<；0.05)，而布地奈德(腹内注射116mumol/kg或气管灌流26mumol/kg)则无作用。两次重复暴露于TDI3NL(第1天和第8天)使动物对TDI高反应，因此在第15天，先前亚阈值剂量的TDI0.3NL在暴露后5小时和17小时都产生了显著的渗出(P<；0.001至P<；0.01)。同样，重复两次皮肤暴露于大剂量TDI(20毫升)，降低了使用TDI刺激气管的阈值。布地奈德(2.6摩尔/公斤口服)在局部呼吸道“致敏”方案(第1-14天)期间每日给予，显著降低对随后0.3nL TDI激发剂量的反应(P<；0.05)。每日给予茶碱(100mumol/kg)或安非他林(50mumol/kg)的效果均不显著。我们的结论是，两个单独的呼吸道暴露于低炎症剂量的TDI会使呼吸道粘膜对该制剂的敏感性增加约10倍。黄嘌呤类药物仅能减轻急性炎症反应。糖皮质激素治疗可减少对TDI反应增强的发展，但不能减少急性炎症反应。
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 < 0.001 to P < 0.01, 5 and 17 hr after exposure). Pretreatment with intravenous enprofylline (25 mumol/kg) reduced (P < 0.05) the acute response measured at 5 hr whereas budesonide (116 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 < 0.001 to P < 0.01). Similarly, two repeated dermal exposures to a large dose of TDI (20 mul) 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 < 0.05). The effects of daily treatments with either theophylline (100 mumol/kg) or enprofylline (50 mumol/kg) were not significant. We conclude that two separate airway exposures to a low inflammatory dose of TDI increased about tenfold the airway mucosal sensitivity to this agent. Only the acute inflammatory response was reduced by xanthines. The development of increased responsiveness but not the acute inflammatory response to TDI was reduced by glucocorticoid treatment.