Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau J C
Department of Dermatology, Hôpital Henri Mondor, Université Paris XII, Créteil, France.
Br J Dermatol. 1998 Dec;139(6):1026-32. doi: 10.1046/j.1365-2133.1998.02559.x.
Hypersensitivity syndrome (HSS) usually refers to severe drug eruption associated with systemic symptoms and eosinophilia. Interleukin (IL)-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 eosinophilia 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 GM-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.
超敏反应综合征(HSS)通常指伴有全身症状和嗜酸性粒细胞增多的严重药物疹。白细胞介素(IL)-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,继发于寄生虫感染或特发性嗜酸性粒细胞增多症的嗜酸性粒细胞增多患者血液中的IL-5水平会升高,但尚未在药物性嗜酸性粒细胞增多症中进行评估。我们研究的目的是确定IL-5、IL-3和GM-CSF是否与药物性HSS患者的嗜酸性粒细胞增多有关。通过酶联免疫吸附测定法(ELISA)检测了7例药物性HSS患者、8例与嗜酸性粒细胞增多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患者血浆中的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的IL-5水平均正常,7例HSS患者中有5例升高。在后一组患者中,IL-5水平在嗜酸性粒细胞计数达到最高值前几天达到峰值,即使嗜酸性粒细胞增多持续存在,IL-5水平也会在几天内恢复正常。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。在任何组的任何时间均未检测到IL-3和GM-CSF。我们的结果表明,IL-5与药物相关的嗜酸性粒细胞增多有关。由于IL-5的产生仅参与反应的早期阶段,因此提示IL-5主要来源于活化的淋巴细胞而非嗜酸性粒细胞。我们的结果支持了先前体外研究结果的临床相关性。需要进一步研究以测试检测疑似药物和/或其代谢产物刺激的患者淋巴细胞产生IL-5的试验是否有助于确定与嗜酸性粒细胞增多相关的药物性反应的因果关系。