Enhancement of allograft acceptance by combined dexmedetomidine and rapamycin.

BACKGROUND Dexmedetomidine, an α2-adrenoceptor agonist, is known for its sedative effects and unique pharmacological mechanism. Research increasingly emphasizes its potential to modulate immune responses. Further investigation is needed to fully understand how dexmedetomidine influences T cell differentiation and its potential synergy with tolerance-promoting agents. This study aims to explore a new approach to enhance allograft acceptance by combining dexmedetomidine with the mTOR inhibitor rapamycin. METHODS The effects of both drugs on T cell proliferation, regulatory T cell preservation, and allograft survival were examined through both in vitro and in vivo animal experiments, including a fully MHC-mismatched mouse skin transplantation model. The study also evaluated the effect of combined drugs on immune memory via retransplantation surgery. RESULTS Our data demonstrate that combining dexmedetomidine with rapamycin effectively inhibits T cell proliferation. This combination also increases the frequency of regulatory T cells, thereby preserving immune regulation. Furthermore, dual therapy significantly extends the median survival time (MST) of the skin compared to dexmedetomidine, or rapamycin alone or no treatment (20 vs. 12 days, p < 0.001; 20 vs. 16 days, p < 0.05; 20 vs. 7 days, p < 0.0001). Similarly, mice treated with the combination therapy have notably prolonged MST of the second allogenic graft, compared to no treatment (11 days versus 7.5 days, p < 0.001). CONCLUSION Our findings highlight the potential of combining dexmedetomidine with mTOR inhibitors to enhance graft acceptance and reduce memory responses.

• Publication year

  2025

• Venue

  Transplant Immunology

• Publication date

  2025-10-14

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.trim.2025.102313PMID 41101650
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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