Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome

Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome
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DOI:
10.1046/j.1365-2133.1998.02559.x
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发表时间:
1998-12-01
影响因子:
10.3
通讯作者:
Roujeau, JC
Roujeau, JC
中科院分区:
医学1区
文献类型:
--
作者:
Choquet-Kastylevsky, G;Intrator, L;Roujeau, JC

文献摘要

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过敏综合征(HSS)通常是指伴有全身症状和嗜酸性粒细胞增多的严重药疹。白细胞介素(a)-5在IL-3和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的帮助下调节嗜酸性粒细胞计数。据报道,在继发于寄生虫感染或特发性嗜酸性粒细胞增多的患者中,血液IL-5水平升高。但从未在药物性嗜酸性粒细胞增多症中进行评估。我们的研究目的是确定IL-5、IL-3和GM-CSF是否参与药物性HSS患者嗜酸性粒细胞增多。采用ELISA法检测了7例药物性HSS患者、8例与嗜酸性粒细胞增多症无关的皮肤药物不良反应患者和5例与药物治疗无关的嗜酸性粒细胞增多症患者的血浆IL-3、IL-5和GM-CSF水平。8例无嗜酸性粒细胞增多的药疹患者IL-5水平均正常,7例HSS患者中有5例IL-5水平升高。在后者患者中,IL-5水平在嗜酸性粒细胞计数最高前几天达到峰值,并在几天内恢复正常,即使嗜酸性粒细胞持续存在。在与药物治疗无关的嗜酸性粒细胞增多患者中,IL-5水平虽然显著升高,但仍低于HSS患者。IL-3和GR - csf在任何组、任何时间均未检测到。我们的研究结果表明IL-5参与了药物相关性嗜酸性粒细胞增多。由于IL-5的产生仅参与反应的早期阶段,提示IL-5主要来源于活化的淋巴细胞而非嗜酸性粒细胞。我们的结果支持先前体外研究结果的临床相关性。在可疑药物和/或其代谢物刺激下患者淋巴细胞产生IL-5的测定是否有助于确定与嗜酸性粒细胞增多相关的药物诱导反应的因果关系,还需要进一步的研究来检验。
Hypersensitivity syndrome (HSS) usually refers to severe drug eruption associated with systemic symptoms and eosinophilia. Interleukin (a)-5 regulates eosinophil counts with the help of IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Blood IL-5 levels have been reported to be increased in patients with eosinophila secondary to parasitic infections or idiopathic eosinophilia. but have never been evaluated in drug-induced eosinophilia. The aim of our study was to determine whether IL-5, IL-3 and GM-CSF are involved in eosinophilia in patients with drug-induced HSS. Plasma levels of IL-3, IL-5 and GM-CSF were assayed by ELISA in seven patients with drug-induced HSS, in eight patients with cutaneous adverse drug reactions not associated with eosinophilia, and in five patients with eosinophilia unrelated to drug treatment. IL-5 levels were normal in all eight patients with drug eruptions without eosinophilia, and increased in five of the seven patients with HSS. In the latter patients, IL-5 levels peaked several days before highest eosinophil counts were noted, and returned to normal within a few days, even when eosinophilia persisted. In patients with eosinophilia unrelated to drug treatment, IL-5 levels, although significantly increased, remained lower than in HSS patients. IL-3 and GR I-CSF could not be detected in any group, at any time. Our results show that IL-5 is involved in drug-related eosinophilia. As IL-5 production was only Involved in the early stages of the reaction, it is suggested that IL-5 mainly derives from activated lymphocytes rather than eosinophils. Our results support the clinical relevance of previous in vitro findings. Further studies are needed to test whether assays of IL-5 production by lymphocytes of patients stimulated by the suspected drug and/or its metabolites, are useful in establishing causality in drug-induced reactions associated with eosinophilia.