Pasquale C P, Lima M C, Bandeira-Melo C, Cordeiro R S, Silva P M, Martins M A
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Eur J Pharmacol. 1999 Feb 26;368(1):67-74. doi: 10.1016/s0014-2999(99)00010-2.
We have studied the effect of local and systemic treatment with dexamethasone for prevention of the pleural eosinophilia triggered by allergen in actively sensitised Wistar rats. Parallel changes in blood and marrow eosinophil numbers were assessed for comparison. The intrapleural (i.pl.) injection of ovalbumin into ovalbumin-sensitised animals led to a long-lasting pleural fluid eosinophilia which peaked from 24 to 72 h post-challenge. At these time points, there was a significant 2- to 3-fold increase in the blood eosinophil numbers, whereas the bone marrow number of mature eosinophils remained unaltered. Systemic treatment with dexamethasone (0.05-0.5 mg/kg, i.p.) abolished the pleural and blood eosinophilia observed 24 and 48 h post-challenge, also causing a significant reduction in marrow eosinophil numbers. Despite being unable to alter blood and bone marrow eosinophil numbers, the local i.pl. administration of dexamethasone (2.5-10 microg/cavity) inhibited dose dependently the allergen-induced pleural eosinophil influx at 24 h but not at 48 h post-challenge. This treatment also shortened the time course of eosinophil accumulation in the pleural space from the 48 h time point on. We conclude that the effect of systemic but not of local treatment with dexamethasone on allergen-induced eosinophil recruitment is well correlated with the inhibition of eosinophil production in bone marrow. In contrast, low amounts of dexamethasone injected into the pleural space seem to affect locally eosinophil recruitment and survival.
我们研究了地塞米松局部和全身治疗对预防主动致敏的Wistar大鼠中由过敏原引发的胸膜嗜酸性粒细胞增多的作用。评估血液和骨髓嗜酸性粒细胞数量的平行变化以作比较。向卵清蛋白致敏的动物胸腔内（i.pl.）注射卵清蛋白会导致持久的胸腔积液嗜酸性粒细胞增多，在激发后24至72小时达到峰值。在这些时间点，血液嗜酸性粒细胞数量显著增加2至3倍，而成熟嗜酸性粒细胞的骨髓数量保持不变。地塞米松全身治疗（0.05 - 0.5 mg/kg，腹腔注射）消除了激发后24和48小时观察到的胸膜和血液嗜酸性粒细胞增多，同时也导致骨髓嗜酸性粒细胞数量显著减少。尽管无法改变血液和骨髓嗜酸性粒细胞数量，但胸腔内局部注射地塞米松（2.5 - 10微克/腔）在激发后24小时剂量依赖性地抑制了过敏原诱导的胸膜嗜酸性粒细胞流入，但在48小时时没有抑制作用。这种治疗还从48小时时间点开始缩短了胸膜腔中嗜酸性粒细胞积聚的时间进程。我们得出结论，地塞米松全身治疗而非局部治疗对过敏原诱导的嗜酸性粒细胞募集的作用与骨髓中嗜酸性粒细胞生成的抑制密切相关。相比之下，注入胸腔的少量地塞米松似乎局部影响嗜酸性粒细胞的募集和存活。
