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.

Skin-Homing IL-13-Producing T Cells Expand in the Circulation of Patients with Drug Rash with Eosinophilia and Systemic Symptoms

“…Thus, serum TARC levels may represent a potential biomarker of DRESS. Consistent with previous reports [9] , the results of the present study demonstrate elevated serum TARC levels in patients with DRESS. Moreover, the proportion of IL-13-producing T cells was strongly correlated with serum TARC levels, suggesting that the proportion of IL-13-producing T cells may be related to DRESS disease severity.…”

“…T effector lymphocytes have been classified into several subsets, including T helper 1 (Th1) cells, Th2 cells, and Th17 cells, based on cytokine production profiles [7,8] . In patients with DRESS, peripheral blood eosinophilia and elevated serum levels of Th2 cytokines and chemokines, such as interleukin-5 (IL-5) [9] and thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17, are commonly observed [10] , indicating that the Th2-type immune response may be involved in the pathogenesis of DRESS. However, there are no detailed data regarding the T-cell phenotypes contributing to the pathogenesis of DRESS.…”

Atypical DRESS Syndrome Induced by Lenalidomide in Chronic Hemodialysis

“…Defective drug detoxification process resulting in accumulation of toxic metabolites has also been suggested [12]. Furthermore, drug specific CD4+ and CD8+ T-cells have been shown to expand during the acute phase of the disease leading to the release of pro-inflammatory interleukin 5 [13]. Intriguingly, the expansion of regulatory T-cells has also been associated to HHV-6 reactivation and DRESS syndrome development [14].…”

Sequential appearance of four clinical delayed drug hypersensitivity in the same patient

“…11 IL-5 secreting T cells are decisive for the eosinophilia of DRESS, but the simultaneous hepatitis is linked to cytotoxic T cells. 12,13 This complexity is mirrored in the appearance of overlap syndromes, where two T cell functions dominate the clinical picture together. Such an overlap syndrome occurred also in the patient described, as her AGEP like skin reaction occurred together with signs of a massive eosinophilia (due to activation of IL-5 secreting T cells) and signs of liver damage (activation of cytotoxic T cells), both typical for DRESS.…”

“…Such an overlap syndrome occurred also in the patient described, as her AGEP like skin reaction occurred together with signs of a massive eosinophilia (due to activation of IL-5 secreting T cells) and signs of liver damage (activation of cytotoxic T cells), both typical for DRESS. 12,13 c) The last DHR symptom was a bullous skin reaction with massive keratinocyte detachment as seen in TEN. It appeared after drug therapy has already been stopped for two days, and extended further in the next days.…”