Comparison of Immune Responses Induced by Deferoxamine and Deferasirox

Abstract

Background: The iron chelating agents (ICA) have various biological effects besides iron chelation. We investigated the immunomodulatory effects of Deferasirox (DFS) compared to Deferoxamine (DFO). Methods: Spleen cells (SP) were obtained from 5 week-old C57/BL6 (H-2b). The cytotoxicity of ICAs was examined using the CCK8 method. For the cell proliferation assay, SP were cultured with irradiated in addition to 10, 50, 100μM of DFS or DFO and 200ng/mL of cyclosporin A (CSA). Cytokines and nitrite levels were evaluated from supernatants by ELISA. Results: The viability of ICA was reported to be over 100%. Both DFS and DFO inhibited cell proliferation in a manner comparable to CSA. Cell proliferation without iron was reduced at the concentration of 100μM of DFO. With iron treatment, the reduction of the stimulation index was dependent on DFO concentrations. DFS decreased the proliferation without reference to the concentrations. After stimulation of phytohemagglutinin, the nitrite concentrations increased with iron. With lipopolysaccharides, the nitrite levels were higher in DFO with iron than control, but similar in DFS regardless of iron treatment. The levels of interleukin-2 were not different. Interleukin-10 was more abundantly produced in 50μM of DFO compared to DFS. Transforming growth factor-β was higher in DFS than DFO at the low concentration, but opposite at the high concentration. Conclusion: These data suggested that both iron chelating agents possessed immune suppressive effects comparable to CSA. The immunosuppressive effect of DFS may be distinct from DFO. More experiments are required to determine the exact mechanism of the immunosuppressive effect of DFS.