Amniai L, Biet F, Marquillies P, Locht C, Pestel J, Tonnel A-B, Duez C
INSERM, Institut National de la Santé et de la Recherche Médicale U774, Lille 59019, France.
J Biomed Biotechnol. 2007;2007:67276. doi: 10.1155/2007/67276.
Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D20-22) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.
虽然卡介苗在小鼠模型中可抑制过敏性气道反应，但白细胞介素-18根据其所处环境会产生相反的作用。因此，我们构建了一种能产生小鼠白细胞介素-18的卡介苗菌株（卡介苗-白细胞介素-18），并评估了其预防小鼠哮喘样反应的效果。通过腹腔注射卵清蛋白（OVA）-明矾对BALB/cByJ小鼠进行致敏（第1天和第10天），并用OVA气雾剂进行初次激发（第20 - 22天）和二次激发（第62、63天）。在每次免疫前1小时（第1天和第10天）腹腔注射卡介苗或卡介苗-白细胞介素-18。在初次和二次激发后，卡介苗-白细胞介素-18和卡介苗均显示出类似地抑制气道高反应性的发展、黏液分泌、嗜酸性粒细胞浸润以及支气管肺泡灌洗液中局部Th2细胞因子的产生。这些数据表明，在分枝杆菌感染的情况下，白细胞介素-18不会增加过敏性气道反应，并提示卡介苗-白细胞介素-18和卡介苗能够预防局部Th2反应的发展，因此即使在再次刺激后也能抑制变应原诱导的气道反应。
