IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice
IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice
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DOI：
10.1152/ajplung.2000.278.4.l667
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发表时间：
2000-04-01
影响因子：
4.9
通讯作者：
Sur, S
中科院分区：
文献类型：
--
作者：
van Scott, MR;Justice, JP;Sur, S
我们研究了白介素10对变应原诱导的Th2细胞因子的产生、嗜酸性炎症和呼吸道反应性的影响。用豚草(RW)对小鼠进行致敏，豚草(RW)吸附在明胶上，气管内滴注过敏原。致敏和RW激发使BAL液中IL-10浓度在72小时内从检测不到的水平增加到60pg/ml，RW激发时气管内注入25 ng重组小鼠IL-10进一步增加BAL，BAL液中IL-10浓度增加到440pg/ml，而BAL液中IL-4、IL-5和干扰素-γ水平下降40-85%，嗜酸性粒细胞数下降70%(P<；0.0001)。出乎意料的是，同样的IL-10治疗增加了自发呼吸的小鼠对乙酰甲胆碱的反应性，这些小鼠已经被RW致敏和挑战(P<；0.001)。用PBS攻击幼稚动物或RW致敏小鼠的IL-10治疗未能增加呼吸道反应性，表明IL-10只有在与过敏性致敏和挑战一起使用时才能诱导气道反应性增加。结果表明，IL-10降低Th2细胞因子水平和嗜酸性炎症，但增强气道高反应性。因此，尽管IL-10具有强大的抗炎活性，但它可能会导致哮喘患者肺功能的下降。
We investigated the effects of interleukin (IL)-10 administration on allergen-induced Th2 cytokine production, eosinophilic inflammation, and airway reactivity. Mice were sensitized by intraperitoneal injection of ragweed (RW) adsorbed to Alum and challenged by intratracheal instillation of the allergen. Sensitization and challenge with RW increased concentrations of IL-10 in bronchoalveolar lavage (BAL) fluid from undetectable levels to 60 pg/ml over 72 h. Intratracheal instillation of 25 ng of recombinant murine IL-10 at the time of RW challenge further elevated BAL, fluid IL-10 concentration to 440 pg/ml but decreased BAL fluid IL-4, IL-5, and interferon-gamma levels by 40-85% and eosinophil numbers by 70% (P < 0.0001). Unexpectedly, the same IL-10 treatment increased airway reactivity to methacholine in spontaneously breathing mice that had been sensitized and challenged with RW (P < 0.001). IL-10 treatment in naive animals or RW-sensitized mice challenged with PBS failed to increase airway reactivity, demonstrating that IL-10 induces an increase in airway reactivity only when it is administered in conjunction with allergic sensitization and challenge. The results demonstrate that IL-10 reduces Th2 cytokine levels and eosinophilic inflammation but augments airway hyperreactivity. Thus, despite its potent anti-inflammatory activity, IL-10 could contribute to the decline in pulmonary function observed in asthma.