Yonsei Med J.  2022 Feb;63(2):158-165. 10.3349/ymj.2022.63.2.158.

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

• Kim SJ
• Kim JY
• Kim EJ
• Lee H
• Cho Y
• Kim MS
• Kim YS
• Kim BS
• Huh KH

• KMID: 2525259
• DOI: http://doi.org/10.3349/ymj.2022.63.2.158

Abstract

Purpose
The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, 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-2^d ) donors to C57BL/6 (H-2^b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal 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 assay 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⁺ CD44^hi 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.

Keyword

Immunomodulation; Immunomodulation; dexamethasone; T cells; dendritic cells; cardiac transplantation