The Immunomodulating Effects of Thalidomide and Dexamethasone in a Murine Cardiac Allograft Transplantation Model

Soo Jin Kim, Joon Ye Kim, Eun Jee Kim, Hyojung Lee, Yuri Cho, Myoung Soo Kim, Yu Seun Kim, Beom Seok Kim, Kyu Ha Huh

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimula-tory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. Materials and Methods: Intraabdominal transplant of cardiac allografts from BALB/c (H-2d) donors to C57BL/6 (H-2b) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by in-traperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent as-say on day 7. Results: The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4+FOXP3+/CD4+CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. Conclusion: These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalYonsei medical journal
Volume63
Issue number2
DOIs
Publication statusPublished - 2022 Feb

Bibliographical note

Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI18C0629).

Publisher Copyright:
© Yonsei University College of Medicine 2022.

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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