Comparison of Immune Responses Induced by Deferoxamine and Deferasirox

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.

[1]  Jun Yeol Choi,et al.  Desferrioxamine (DFX) has genotoxic effects on cultured human lymphocytes and induces the p53-mediated damage response. , 2007, Toxicology.

[2]  J. Golenser,et al.  IRON CHELATORS: CORRELATION BETWEEN EFFECTS ON PLASMODIUM SPP. AND IMMUNE FUNCTIONS , 2006, The Journal of parasitology.

[3]  A. Cohen,et al.  New advances in iron chelation therapy. , 2006, Hematology. American Society of Hematology. Education Program.

[4]  E. Eracleous,et al.  Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations. , 2005, Current medicinal chemistry.

[5]  N. Andrews,et al.  Iron homeostasis and inherited iron overload disorders: an overview. , 2004, Hematology/oncology clinics of North America.

[6]  R. Crichton,et al.  Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine. , 2003, Journal of inorganic biochemistry.

[7]  Young-sil Yoon,et al.  Iron chelation-induced senescence-like growth arrest in hepatocyte cell lines: association of transforming growth factor beta1 (TGF-beta1)-mediated p27Kip1 expression. , 2002, The Biochemical journal.

[8]  R. Crichton,et al.  Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. , 2002, Journal of inorganic biochemistry.

[9]  J. Marx.  Iron and infection: competition between host and microbes for a precious element. , 2002, Best practice & research. Clinical haematology.

[10]  C. Beaumont,et al.  Iron metabolism, free radicals, and oxidative injury. , 2001, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[11]  G. Weiss,et al.  Regulatory interactions between iron and nitric oxide metabolism for immune defense against Plasmodium falciparum infection. , 2001, The Journal of infectious diseases.

[12]  S. Oppenheimer.  Iron and its relation to immunity and infectious disease. , 2001, The Journal of nutrition.

[13]  G. Kontoghiorghes,et al.  Transfusional iron overload and chelation therapy with deferoxamine and deferiprone (L1). , 2000, Transfusion science.

[14]  A. Hoffbrand,et al.  Iron chelators induce apoptosis in proliferating cells , 1995, British journal of haematology.

[15]  C. Borgna-Pignatti,et al.  9 Clinical manifestations and therapy of transfusional haemosiderosis , 1994 .

[16]  C. Borgna-Pignatti,et al.  Clinical manifestations and therapy of transfusional haemosiderosis. , 1994, Bailliere's clinical haematology.

[17]  J. Kupiec-Weglinski,et al.  Iron chelation suppresses mononuclear cell activation, modifies lymphocyte migration patterns, and prolongs rat cardiac allograft survival in rats. , 1993, Transplantation.

[18]  K. Nouri-Aria,et al.  Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine. , 1990, Immunology.

[19]  J. Cambier,et al.  Desferoxamine blocks IL 2 receptor expression on human T lymphocytes. , 1986, Journal of immunology.

[20]  P. Doherty,et al.  Effect of an iron-chelating agent on lymphocyte proliferation. , 1984, The Australian journal of experimental biology and medical science.

[21]  E. Romano,et al.  The effect of desferrioxamine on the proliferative response of rat lymphocytes stimulated with various mitogens in vitro. , 1984, Immunopharmacology.

[22]  J. G. Cory,et al.  Effect of iron-chelating agents on inhibitors of ribonucleotide reductase. , 1981, Biochemical pharmacology.