Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
Int Arch Allergy Immunol. 2012;158(4):369-74. doi: 10.1159/000335122. Epub 2012 Apr 4.
Blockade of tyrosine kinase signaling by masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, can modulate allergic airway inflammation, but effects on lung mechanics have not been well characterized. We hypothesized masitinib would decrease airway eosinophilia and consequently improve pulmonary mechanics in a feline allergic asthma model.
Asthma was induced in 12 cats using Bermuda grass allergen (BGA). Cats received 50 mg/day oral masitinib or placebo. Bronchoalveolar lavage fluid (BALF) was analyzed for eosinophils, total protein (TP) and BGA-specific IgE. Ventilator-acquired mechanics after methacholine (MCh) challenge determined MCh concentration needed to increase baseline airway resistance by 200% (EC(200)R(aw)), positive end expiratory occlusion pressure (PEEP) and end inspiratory breath hold pressure (P(plat)). An inverse correlate of respiratory system compliance P(plat)-PEEP was also calculated. Data were analyzed using the Wilcoxon test, with one-tailed significance set at p < 0.1.
After 4 weeks, percent eosinophils in BALF was lower in masitinib-treated cats (7 ± 9%) versus controls (30 ± 27%, p = 0.023). BALF TP significantly differed (p = 0.047) between groups, decreasing with masitinib and increasing with placebo. BALF BGA-specific IgE was unaffected by masitinib. Both groups showed an improvement in EC(200)R(aw) (masitinib, p = 0.015; control, p = 0.078) but no significant change in PEEP after 4 weeks. Masitinib-treated cats demonstrated decreased P(plat) (p = 0.033) and P(plat)-PEEP (p = 0.075) at week 4, suggesting an improvement in respiratory compliance.
Masitinib reduced BALF eosinophilia and TP, indicating improved airway inflammation and edema, and improved P(plat) and P(plat)-PEEP, suggesting benefit to respiratory compliance influenced by airway inflammation/edema. Masitinib deserves further study in humans with chronic allergic asthma.
通过阻断 c-kit/PDGF 受体酪氨酸激酶，马替尼可以调节过敏性气道炎症，但对肺力学的影响尚未得到很好的描述。我们假设马替尼可以减少气道嗜酸性粒细胞，并因此改善猫变应性哮喘模型中的肺力学。
用百慕大草过敏原（BGA）诱导 12 只猫发生哮喘。猫每天接受 50mg 口服马替尼或安慰剂。分析支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞、总蛋白（TP）和 BGA 特异性 IgE。在给予乙酰甲胆碱（MCh）后，通过呼吸机获得的力学来确定增加基础气道阻力 200%所需的 MCh 浓度（EC（200）R（aw））、呼气末正压（PEEP）和吸气末保持呼气暂停压力（P（plat））。还计算了呼吸系统顺应性 P（plat）-PEEP 的倒数。数据使用 Wilcoxon 检验进行分析，单侧检验显著性水平设为 p < 0.1。
4 周后，马替尼治疗组猫 BALF 中的嗜酸性粒细胞百分比（7 ± 9%）低于对照组（30 ± 27%，p = 0.023）。两组间 BALF TP 差异显著（p = 0.047），马替尼治疗组降低，安慰剂组升高。BALF BGA 特异性 IgE 不受马替尼影响。两组 EC（200）R（aw）均有所改善（马替尼，p = 0.015；对照组，p = 0.078），但 4 周后 PEEP 无显著变化。马替尼治疗组猫在第 4 周时 P（plat）（p = 0.033）和 P（plat）-PEEP（p = 0.075）降低，提示呼吸顺应性改善。
马替尼降低 BALF 嗜酸性粒细胞和 TP，表明气道炎症和水肿改善，改善 P（plat）和 P（plat）-PEEP，提示气道炎症/水肿对呼吸顺应性有改善作用。马替尼值得在慢性过敏性哮喘患者中进一步研究。
