Volume 4 Supplement 3
Drugs responsible of DRESS syndrome regulate IL-10 and TNF-α secretion
© Calbo et al; licensee BioMed Central Ltd. 2014
Published: 18 July 2014
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced reaction that involves both the skin and the viscera. Several herpesvirus family members like EBV or HHV-6 can be detected coincidently with various clinical symptoms in DRESS. In addition, we have previously identified activated EBV specific cytotoxic CD8+ T cells as major actors in the pathophysiology of DRESS. In vitro, we have showed that DRESS inducer drugs increase production of EBV virus only on B-LCL lines from DRESS patients. However, drug effect on cytokines secretion has not been studied. Gene expression profiling of DRESS patients' PBMC revealed that IL-10 and TNF-α were two of the most upregulated mRNA. We thus measured IL-10 and TNF-α secretion levels in DRESS patients' serum and B-LCL lines following incubation with drugs.
EBV-B cell lines were obtained after incubation of B cells from DRESS patients or healthy donors with EBV virus. Also, DRESS patients and healthy donors PBMC and serum were included in the study. We analysed the presence of IL-10 by ELISA, FACS and QPCR, and the presence of TNF-α by ELISA and FACS.
We show that DRESS patients have an increase of IL-10 and TNF-α in their serum. IL-10 is not secreted by CD4+ T cells but DRESS patients have regulatory B cells which, under stimulation, produce two times more IL-10 than B cells from healthy controls. In vitro, we demonstrate that some DRESS inducer drugs reduce significantly the IL-10 secretion in B-LCL from DRESS patients but not from healthy donors by sequestering IL-10. Interestingly, the same observation was obtained for TNF-α in DRESS patients and healthy donors B-LCL, with however differential effect depending of the drugs regarding the sequestering of TNF-α.
the balance between IL-10 and TNF-α is affected by DRESS inducer drugs specifically in DRESS patient. These findings allow a better understanding of the physiopathology of the DRESS syndrome.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.