Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Sci Rep. 2021 Sep 28;11(1):19221. doi: 10.1038/s41598-021-98538-z.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / drug effects
  • Allografts / immunology
  • Animals
  • Brain Death / immunology*
  • Disease Models, Animal
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Humans
  • Liver / drug effects
  • Liver / immunology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / methods
  • Male
  • Rats
  • Rats, Inbred Lew
  • Thalidomide / administration & dosage*
  • Tissue and Organ Harvesting / methods*


  • Thalidomide