Objectives: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory effects and dexamethasone (DX) has been reported that it also reduces inflammation and inhibits inflammatory cytokine production. It has been reported by many research groups that combinatorial therapy of TM and DX is clinically used in treatment for multiple myeloma and lupus nephritis, and we also previous examined the mechanisms responsible for its effects. In our previous study, we have shown that TM/DX combinatorial treatments have immune-modulatory functions and affect each CD4⁺ T cell subset differently and specifically, by regulating the expression of co-stimulatory molecules on CD4⁺ T cells. In this study, we determined that TM/DX combinatorial treatments affect not only T cells, but other immune cells.
Methods: Spleens were isolated from eight-week-old normal C57BL/6 mice received chow containing either no drug, TM, DX, or TM/DX for one week. Homogenized splenocytes were then stained with phycoerythrin (PE)-Cy7-conjugated anti-mouse CD8, peridinin chlorophyll protein (PerCP)- cyanine (Cy) 5.5-conjugated anti-mouse CD19, and PerCP-Cy5.5-conjugated anti-mouse CD11c antibodies and population of CD8⁺ T cells, CD19⁺ B cells, and CD11c⁺ dendritic cells (DCs) were quantified by flow cytometry.
Results: CD8 T cell population was significantly increased in DX and TM/DX groups, which we attribute to the effect of DX. CD19⁺ cell population, however, showed the exact opposite results that it significantly decrease in DX and TM/DX groups, which also resulted from the effect of DX. DC population was slightly increased upon DX, but upon TM/DX combinatorial treatment, DC population was increased about two-fold compared to that of CTL, TM, and DX groups.
Conclusion: Considering the results and the previously reported data, we suggest that TM/DX combinatorial treatment plays enhanced immune-modulatory role by having the varying effect on different immune cells. Compared to immunosuppressant drugs, which reduce T cell and immune cell populations regardless of their subsets or types, TM/DX combinatorial treatment showed clear modulating effects and can be potentially used as a viable immune-modulatory therapy following transplantation. Further study will be conducted, largely focusing on the drug effect on DCs, to determine the underlying molecular links between the TM/DX’s effects and immune cells.