title: Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome.
abstract: 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.
authors.affiliation: Department of Dermatology, Hôpital Henri Mondor, Université Paris XII, Créteil, France. choquet@cimac-res.univ-lyon1.fr
authors.forename: G
authors.initials: G
authors.lastname: Choquet-Kastylevsky
authors.forename: L
authors.initials: L
authors.lastname: Intrator
authors.forename: C
authors.initials: C
authors.lastname: Chenal
authors.forename: H
authors.initials: H
authors.lastname: Bocquet
authors.forename: J
authors.initials: J
authors.lastname: Revuz
authors.forename: J C
authors.initials: JC
authors.lastname: Roujeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004342:Drug Hypersensitivity / Q000378:metabolism*; D004802:Eosinophilia / Q000209:etiology* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged