Townley Robert G, Gendapodi Pradeep R, Qutna Nidal, Evans Joseph, Romero Francisco A, Abel Peter
Division of Allergy/Immunology, Creighton University, Omaha, Nebraska 68131, USA.
Ann Allergy Asthma Immunol. 2009 Mar;102(3):190-7. doi: 10.1016/S1081-1206(10)60080-4.
Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR.
To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists.
The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol.
IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice.
The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.
氟替卡松可影响气道支气管高反应性（BHR），并增强β-肾上腺素能激动剂诱导的支气管扩张和支气管保护作用。然而，白细胞介素13（IL-13）可诱导BHR。
验证氟替卡松在变应原致敏或给予IL-13后抑制BHR以及氟替卡松恢复β-激动剂的支气管扩张和支气管保护作用的假设。
测定BALB/c小鼠中由IL-13或卵清蛋白诱导的对乙酰甲胆碱的BHR，并计算引起呼气增强停顿增加200%的乙酰甲胆碱激发浓度（PC200）。我们将对照小鼠对乙酰甲胆碱的反应与用IL-13受体α2-IgGFc融合蛋白（IL-13Rα2）（一种IL-13阻滞剂）、氟替卡松、沙丁胺醇、沙美特罗、氟替卡松-沙丁胺醇和氟替卡松-沙美特罗治疗后的反应进行比较。
IL-13Rα2（PC200，17.59）完全阻断IL-13诱导的BHR效应（PC200，7.28；P<.005）。IL-13治疗后（PC200，5.90；P<.005），1mg/mL沙丁胺醇（PC200，3.38；P=.33）、氟替卡松（PC200，4.59；P=.40）或氟替卡松加50μg/mL沙美特罗（PC200，5.59；P=.11）均未显示出显著的支气管保护作用。在未致敏小鼠中，氟替卡松加0.25μg/mL沙美特罗（PC200，25.90；P<.005）显示出比单独使用沙美特罗（PC200，11.08；P=.26）显著更强的支气管保护作用。在卵清蛋白致敏小鼠中，氟替卡松加0.3mg/mL沙丁胺醇和氟替卡松加1mg/mL沙丁胺醇比单独使用氟替卡松或沙丁胺醇具有显著更强的保护作用。
在IL-13治疗的小鼠中，氟替卡松、β-激动剂以及氟替卡松加β-激动剂的保护作用明显低于未致敏或卵清蛋白致敏小鼠。
