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Drugs responsible of DRESS syndrome regulate IL-10 and TNF-α secretion
Clinical and Translational Allergy volume 4, Article number: P45 (2014)
Background
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.
Method
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.
Results
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.
Conclusion
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.
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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.
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Calbo, S., Sabbah, B., Janela, B. et al. Drugs responsible of DRESS syndrome regulate IL-10 and TNF-α secretion. Clin Transl Allergy 4 (Suppl 3), P45 (2014). https://doi.org/10.1186/2045-7022-4-S3-P45
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DOI: https://doi.org/10.1186/2045-7022-4-S3-P45
Keywords
- Gene Expression Profile
- Healthy Donor
- Eosinophilia
- Cytokine Secretion
- Systemic Symptom