Milanese Manlio, Riccio Anna Maria, Gamalero Cinzia, De Giovanni Barbara, Brichetto Lorenzo, Baroffio Michele, Crimi Emanuele, Brusasco Vito, Canonica Giorgio Walter
Department of Internal Medicine, University of Genoa, Genoa, Italy.
Ann Allergy Asthma Immunol. 2005 Feb;94(2):273-8. doi: 10.1016/S1081-1206(10)61308-7.
In our previous in vitro model, allergen incubation of passively sensitized human airways reduced the response to salbutamol. However, whether cytokines play a role in this model is still unknown.
To investigate interleukin 1beta and tumor necrosis factor a expression in allergen-challenged human airways.
Nonasthmatic airways (n = 13) were passively sensitized by overnight atopic serum incubation and then challenged with allergen for 1 hour (n = 9). After repeated washouts, airways were immersed in physiologic salt solution for 6 hours and finally in formaldehyde for immunohistochemical studies. The effect of co-incubation in anti-interleukin 1beta and anti-tumor necrosis factor a specific neutralizing antibodies on salbutamol response was also studied (n = 4).
No differences were found among control, sensitized, and challenged rings in the number of inflammatory cells. The percentage of basement membrane covered by epithelium was similar in the different conditions. There was a higher percentage of degranulating to total mast cells in allergen-challenged rings than in sensitized rings (P < .001). A significant correlation was observed between allergen-induced contraction and mast cell degranulation (r = 0.88; P < .001). The sensitization procedure was validated by paired allergen-induced contractions. No expression of the 2 cytokines was detectable up to 6 hours after allergen challenge, and specific neutralizing antibodies did not attenuate the impaired response to salbutamol in allergen-challenged rings.
These data suggest that in our in vitro model of allergic inflammation, beta2 pathway dysfunction can occur without cytokine involvement, thus supporting previous results that suggest a role for leukotrienes.
在我们之前的体外模型中，对被动致敏的人呼吸道进行变应原孵育会降低对沙丁胺醇的反应。然而，细胞因子在该模型中是否起作用仍不清楚。
研究白细胞介素1β和肿瘤坏死因子α在变应原激发的人呼吸道中的表达。
通过过夜孵育特应性血清对非哮喘呼吸道（n = 13）进行被动致敏，然后用变应原激发1小时（n = 9）。反复冲洗后，将呼吸道浸入生理盐溶液中6小时，最后浸入甲醛中进行免疫组织化学研究。还研究了抗白细胞介素1β和抗肿瘤坏死因子α特异性中和抗体共同孵育对沙丁胺醇反应的影响（n = 4）。
在对照组、致敏组和激发组的炎症细胞数量上未发现差异。在不同条件下，上皮覆盖的基底膜百分比相似。与致敏环相比，变应原激发环中脱颗粒肥大细胞占总肥大细胞的百分比更高（P <.001）。变应原诱导的收缩与肥大细胞脱颗粒之间存在显著相关性（r = 0.88；P <.001）。通过变应原诱导的配对收缩验证了致敏程序。在变应原激发后6小时内未检测到这两种细胞因子的表达，并且特异性中和抗体并未减弱变应原激发环中对沙丁胺醇受损的反应。
这些数据表明，在我们的过敏性炎症体外模型中，β2途径功能障碍可能在没有细胞因子参与的情况下发生，从而支持了先前提示白三烯作用的结果。
