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Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
- Source :
- Scientific Reports, Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.
- Subjects :
- Drug
Graft Rejection
Male
Brain Death
media_common.quotation_subject
Science
Pharmacology
Article
Transplant immunology
MHC class I
Medicine
Animals
Humans
Electrophoretic mobility shift assay
Intracranial pressure
media_common
chemistry.chemical_classification
Multidisciplinary
biology
business.industry
Immunogenicity
Balloon catheter
Allografts
Liver Transplantation
Rats
Thalidomide
Disease Models, Animal
Enzyme
chemistry
Liver
Rats, Inbred Lew
biology.protein
Tissue and Organ Harvesting
Cytokines
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....c740ab3c682c844540c55609df035fd6