Differential cytokine profiles produced by anti-epileptic drug re-exposure of peripheral blood mononuclear cells derived from severe anti-epileptic drug patients and non-allergic controls

Yuttana Srinoulprasert; Pongsathorn Kumkamthornkul; Papapit Tuchinda; Sattawut Wongwiangjunt; Sith Sathornsumetee; Kowit Jongjaroenprasert; Kanokvalai Kulthanan

doi:10.1016/j.cyto.2022.155951

Differential cytokine profiles produced by anti-epileptic drug re-exposure of peripheral blood mononuclear cells derived from severe anti-epileptic drug patients and non-allergic controls

Cytokine. 2022 Sep:157:155951. doi: 10.1016/j.cyto.2022.155951. Epub 2022 Jun 27.

Authors

Yuttana Srinoulprasert¹, Pongsathorn Kumkamthornkul², Papapit Tuchinda³, Sattawut Wongwiangjunt⁴, Sith Sathornsumetee⁴, Kowit Jongjaroenprasert⁵, Kanokvalai Kulthanan³

Affiliations

¹ Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Electronic address: yuttana.sri@mahidol.ac.th.
² Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
³ Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
⁴ Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
⁵ Adverse Drug Reaction Unit, Pharmacy Department, Siriraj Hospital, Mahidol University, Thailand.

PMID: 35772364
DOI: 10.1016/j.cyto.2022.155951

Abstract

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are the most common severe cutaneous adverse drug reactions (SCARs). Anti-epileptic drugs are one of the most common drugs causing SCARs. Cytokine profiles of SCARs during culprit drug exposure have never been characterized. This study aimed to identify cytokine patterns between SCARs and non-SCARs in epilepsy patients and the patterns of DRESS and SJS/TEN. Epilepsy patients that showed allergic responses to anti-epileptic drugs that manifested as SJS/TEN or DRESS were recruited. Epilepsy patients with no drug allergy symptoms and healthy people were also recruited as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with assigned anti-epileptic drugs according to the lymphocyte transformation test (LTT). LTT and measurement of cytokine levels in supernatants were performed on day six of cell cultivation. This study identified different cytokine expression patterns between SCAR and non-SCAR in epilepsy patients. Significant levels of IL-10, IL-12, IL-17, and GM-CSF were detected in non-SCAR epilepsy. However, the levels of IL-2, IL-5, IL-13, and IFN-gamma were significantly higher in supernatants of PBMCs of DRESS cultivated with AEDs relative to those of SJS/TEN. These cytokine levels were positively correlated with the cell proliferation index. Production of IL-5 and IL-13 was a unique characteristic of DRESS PBMCs. This study was the first to demonstrate distinct differences in cytokine levels between SCAR and non-SCAR PBMCs in epilepsy, which could help explain the immune-pathomechanism of drug hypersensitivity in SCARs. Different patterns of cytokine production and cell proliferation between DRESS and SJS/TEN in AED hypersensitivity were also demonstrated. Production of IL-5 and IL-13 might be a promising marker to define drug hypersensitivity in DRESS.

Keywords: Anti-epileptic drug hypersensitivity; Cytokines; DRESS; Epilepsy; SJS/TEN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines
Drug Hypersensitivity*
Epilepsy* / drug therapy
Humans
Interleukin-13
Interleukin-5
Leukocytes, Mononuclear
Stevens-Johnson Syndrome* / etiology

Substances

Cytokines
Interleukin-13
Interleukin-5