Hsiue T R, Lei H Y, Hsieh A L, Chang H Y, Chen C W
Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Int Arch Allergy Immunol. 1999 Aug;119(4):297-303. doi: 10.1159/000024207.
It is well known that eosinophilic airway inflammation develops after allergen challenge in sensitized humans and animals. However, the detailed time course of suppression of early eosinophilic airway inflammation by pharmacological agents given just after challenge has not been discussed. Therefore, we aimed to evaluate the time course relationship of the suppression of peak eosinophilia by anti-cytokines and pharmacological agents given several hours after the aerosol challenge by a therapeutic approach.
We used crude mite extract as an allergen to create a sensitization and inhalation challenge, and performed bronchoalveolar lavages (BAL) after the inhalation challenge to observe the degree of eosinophilic airway inflammation in guinea pigs. Various anti-cytokines (anti-IL-3 and anti-IL-5) and pharmacological agents (dexamethasone, theophylline, and roxithromycin) were given within several hours after the acute aeorosol challenge to evaluate the suppressive effect on peak eosinophilia in BAL fluid, which occurred 24 h after the challenge.
Our results show that anti-IL-5 and dexamethasone, given within 4 and 8 h after the inhalation challenge, respectively, inhibit the acute allergen-induced peak eosinophilia in BAL fluid. However, anti-IL-3, theophylline, and roxithromycin had no effect on peak eosinophilic airway inflammation after challenge.
These observations suggest that several hours are needed to complete the process of cytokine-induced recruitment of eosinophils from the blood to the airways after acute allergen challenge. This may be the optimal time to administer anti-cytokines and dexamethasone to attenuate the subsequent eosinophilic airway inflammation after acute allergen-induced asthmatic attacks.
众所周知，在致敏的人和动物中，变应原激发后会发生嗜酸性气道炎症。然而，关于激发后立即给予的药物对早期嗜酸性气道炎症抑制作用的详细时间进程尚未见讨论。因此，我们旨在通过一种治疗方法评估激发后数小时给予抗细胞因子和药物对嗜酸性粒细胞峰值抑制作用的时间进程关系。
我们使用粗螨提取物作为变应原进行致敏和吸入激发，并在吸入激发后进行支气管肺泡灌洗（BAL），以观察豚鼠嗜酸性气道炎症的程度。在急性气雾剂激发后数小时内给予各种抗细胞因子（抗IL-3和抗IL-5）和药物（地塞米松、茶碱和罗红霉素），以评估对激发后24小时BAL液中嗜酸性粒细胞峰值的抑制作用。
我们的结果表明，分别在吸入激发后4小时和8小时内给予抗IL-5和地塞米松，可抑制BAL液中急性变应原诱导的嗜酸性粒细胞峰值。然而，抗IL-3、茶碱和罗红霉素对激发后的嗜酸性气道炎症峰值无影响。
这些观察结果表明，急性变应原激发后，细胞因子诱导嗜酸性粒细胞从血液募集到气道的过程需要数小时才能完成。这可能是给予抗细胞因子和地塞米松以减轻急性变应原诱导的哮喘发作后随后嗜酸性气道炎症的最佳时间。
