Saos-2 골육종 세포에서 iron chelating agent, deferoxamine에 의한 apoptosis 유도

박은혜,이효정,이수연,이호근,이대열,황평한,김선영 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.2

Purpose : Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods : To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results : Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion : These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma. 목 적 : 철은 세포 성장과 분화, 전자 전달 반응, 산소 전달, 해독작용 등 여러 가지 중요한 생체 반응에 반드시 필요한 요소로서 종양세포의 성장과 증식에도 절대적으로 필요하다. 최근에 철킬레이트제인 deferoxamine이 악성 구강 각질세포의 성장을 억제하고 세포자멸사를 유도하며, 난소암세포의 증식을 억제하고 세포자멸사를 유도하여 난소암의 성장을 억제하였다고 보고되었다. 그러므로 반복적인 수혈에 의하여 헤모시데린침착증이 발생한 소아 종양 환아에서 deferoxamine이 철을 제거 할 뿐만 아니라 암세포의 세포자멸사를 유도하는지에 대하여 알아보고 세포자멸사를 유도한다면 그 경로에 대하여 알아보고자 하였다. 방 법 : 골육종세포인 Saos-2에서 deferoxamine에 대한 효과를 알아보기 위하여 크리스탈 바이올렛과 트리판 블루 염색으로 세포의 성장 및 증식을 측정하였고, DNA 분획, 핵 응축, 세포주기분석으로 세포자멸사를 분석하였고, 세포자멸사와 관련된 분자들의 발현을 Western hybridization으로 분석하였다. 결 과 : Deferoxamine은 Saos-2 세포에 대하여 시간과 농도에 의존적으로 세포 증식 억제 효과를 나타내었다. 이러한 세포 증식 억제 효과는 DNA 단편화, 핵 응축, 세포주기 분석에서의 A0 기의 증가, PARP의 활성도의 증가 등 세포자멸사가 유도되었음을 알 수 있었다. 또한 Saos-2 세포에서 deferoxamine 처리 후 Akt/PKB의 활성화가 억제되어 caspase 9의 활성화, 그 하류의 caspase 3의 활성화로 이어지는 미토콘드리아 매개되는 경로로 세포자멸사가 유도되었다. 결 론 : 결론적으로 철킬레이트제인 deferoxamine이 세포증식을 억제시키고 세포자멸사를 유도시킴으로써 골육종 세포의 증식을 억제하는 것을 보여주었다. 따라서 반복적 대량 수혈에 의한 철 과부하에 따른 장기손상이 우려되는 각종 소아 종양환자들에서 deferoxamine은 체내 축적된 철을 제거할 뿐만 아니라 종양 환자의 치료에 있어서 항암제 치료의 효과를 증가시킬 수 있는 새로운 치료법으로 개발될 수 있을 것이다.

백서 Paraquat 두여에 의한 간과 폐 조직의 산화성 손상에서 Vitamin C와 Deferoxamine의 항산화 효과에 관한 연구

정연권,서길준,정중식,정성은,최국진,윤여규 대한응급의학회 2000 대한응급의학회지 Vol.11 No.4

Background: The toxicity of paraquat has been known to be caused by oxygen free radicals which leads to the lipid peroxidation and multiple organ failure. Although vitamin C has been known to be a potent antioxidant, recently there are numerous data which have shown that a low dose of vitamin C may act as a prooxidant due to the stimulation of the Fenton reaction with metal ions, which produces hydroxyl radicals. It has been reported that a deferoxamine in paraquat intoxication could reduce the production of the hydroxyl radicals by the inhibition of the Fenton reaction through the reduction of iron ion in tissue. The aim of this study was to evaluate the effect of the high and low dose of vitamin C and deferoxamine on lipid peroxidation and plasma TNF-α in paraquat intoxication. Methods: Female Sprague -Dawley rats were divided into seven groups: control group which was not given paraquat(20 mg/kg), P group which was given paraquat only, PVH group given paraquat and high dose of vitamin C(100 mg/kg), PVL group given paraquat and low dose of vitamin C(10 mg/kg), PVHD given paraquat, high dose of vitamine C and deferoxamine(100 mg/kg), PVLD given paraquat, low dose of vitamin C and deferoxamine, and PD given paraquat and deferoxamine. Animals were killed at 6 and 24 hours after treatment. Malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) contents, catalase activity, plasma TNF-α, and histologic changes in the lung and liver tissue were measured. Results: The lung histology in the PVH and PD or PVHD groups showed the significant decreases in the alveolar edema and interstitial thickness compared to the P group. The liver histololgy in the PVH and PVHD groups demonstrated marked differences in the central venous and sinusoidal dilatation compared to that of the P group. While the MDA levels of the lung and liver in the PVH and PD groups showed the significant reduction compared to that of the P group at 6 hours after treatment, all groups showed the significant changes compared to the P group at 24 hours. There was no significant change of the SOD levels of the lung and liver at 6 hours among all groups. At 24 hours, the SOD levels of the lung in PVH, PVL, and PVHD groups showed the significant increases compared to the P group. The increase of the SOD level in groups combined with deferoxamine, however, revealed a little reduction. The SOD level of the liver in PVH group only significantly increased compared to the P group at 24 hours. There was no significant change of the GSH level of the lung and liver among all groups at 6 hours. At 24 hours, the GSH level of the lung and liver were significantly increased in both PVH and PD group and PVH group, respectively, compared to the P group. Although the catalase activity of the lung was not significantly increased, that of liver was signiflcantly increased in both PVHD and PD groups compared to the P group at 6 hours. The catalase activities of the lung and liver were significantly increased in PVH, PD, and PVHD at 24 hours. The concentrations of the plasma TNF-α were slightly decreased at 6 hours and slightly increased at 24 hours compared to that of the P group, but they were not significant. Conclusion: This study showed that although the low dose of vitamin C had no effect, the high dose of vitamin C revealed a decrease of the MDA level and an increase of SOD, GSH, and catalase activity in the lung and liver tissues, and the effect of the high dose of vitamin C increased with time. The administration of the deferoxamine with or without high dose of vitamin C, however, significantly showed the inhibition of the lipid peroxidation and antioxidant effect and low dose vitamin C decreased the effect of deferoxamine. The effects of the vitamin C and deferoxamine on plasma TNP-α were not clearly shown.

소아 환자에서 deferoxamine에서 deferasirox로 변경 이후 efficacy와 safety 평가

김성환,최미혜,정선회,손인자,이혜숙,안효섭 한국병원약사회 2011 病院藥師會誌 Vol.28 No.3

Deferoxamine has for decades been the standard for iron chelation therapy, but requires administration as a slow continuous subcutaneous or intravenous infusions five to seven times per week, potentially leading to poor compliance, reduced effectiveness. Deferasirox was developed in response to the need for an oral iron chelating agent. Its convenient, once-daily,oral administration schedule offers the potential to improve compliance. However, long-term efficacy and safety remain to be established. This study evaluated the efficacy and safety of deferasirox in pediatric patients who were switched off deferoxamine iron chelating therapy and introduced to deferasirox. It was conducted by method of retrospective chart review. Patients were divided into two groups. Group A(n=22)was constituted of patients who were converted from deferoxamine to deferasirox for their iron chelating therapy. Group B(n=24) was constituted of patients starting iron chelating therapy directly on deferasirox and had never changed. We evaluated the efficacy and the safety of deferasirox through intra-group and inter-group comparisons. The patients in group A, those who were administered deferoxamine, showed a trend of decrease in ferritin levels one month after administration(-222±117.16 ng/ml, p=0.845). In contrast, when the same patients changed their chelating agent to deferasirox, there was a tendency for ferritin levels to increase(+40.67±965.5 ng/ml, p=0.384). However, the ferritin level drop was not statistically different between the drugs (p=0.422). The use of deferasirox in group B decreased ferritin levels more than any other group, but was not statistically significant(-701.5±1687.5 ng/ml, p=0.053). Adverse events were more frequently observed with deferasirox than with deferoxamine in group A(59.1% vs 27.3%). The most common adverse events with deferasirox were gastrointestinal problems and LFT abnormality. On the other hand, skin problems were the most frequent adverse reactions to deferoxamine. Deferasirox showed similar efficacy to deferoxamine in terms of decreasing ferritin levels in pediatric patients. It might be suggested to initiate deferasirox as early as possible due to its efficacy profile and convenient administration regimen. A higher adverse event rate, however,may necessitate for careful monitoring of the patient's clinical status while using deferasirox.

파라쿼트 중독 환자에서 deferoxamine의 치료 효과

허진원 ( Jin Won Huh ),제갈양진 ( Yang Jin Jegal ),홍상범 ( Sang Bum Hong ),오연목 ( Yeon Mok Oh ),심태선 ( Tae Sun Shim ),임채만 ( Chae Man Lim ),이상도 ( Sang Do Lee ),김우성 ( Woo Sung Kim ),김동순 ( Dong Soon Kim ),김원동 ( Won 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.62 No.2

연구배경: 파라쿼트 중독은 다발성 장기부전과 폐섬유화를 유발하여 높은 사망률을 초래한다. 폐섬유화의 약화를 위해 여러 종류의 면역억제제가 사용되었으나 그 치료효과는 다양하다. 철은 파라쿼트로 유발된 산화 스트레스에 의한 폐손상에 중요한 역할은 한다. 본 연구는 파라쿼트 중독의 치료시 철 킬레이트 제제인 deferoxamine의 효과를 보고자 시행되었다. 방법: 2001년 10월부터 2005년 4월까지 파라쿼트 중독으로 내과계중환자실에 입원한 37명 중 28명이 본 연구에 포함되었다. 환자들은 서울아산병원의 파라쿼트 치료 프로토콜에 따라서 치료되었다. 이 중 12명이 추가로 deferoxamine 투여군으로 무작위 분류되었다. 결과: 두 군간의 성별, 나이, 파라쿼트 중독의 정도, 섭취 후 병원까지의 도착 시간 등은 유의한 차이를 보이지 않았다. 파라쿼트 섭취 후 간기능과 신기능의 변화도 유의한 차이를 보이지 않았다. 전체 사망률은 두 군 간의 차이는 없었으나 deferoxamine 투여군에서 대조군과 비교시 호흡부전의 빈도가 높았다(4/7 versus 0/9, p=0.019). 결론: 파라쿼트 중독 시 본 연구에서 적용된 용량과 기간의 deferoxamine (100mg/kg during 24h)은 치료효과가 없을 것으로 사료된다. Background: Paraquat is known to induce oxidant injury that results in multiorgan failure and lung fibrosis. Iron has been considered to play a key role in paraquat-induced oxidant lung injury. This study examined the effect of deferoxamine, an iron-chelating agent, in the treatment of paraquat poisoning. Methods: From September, 2001 to April, 2005, 28 patients with paraquat poisoning who were admitted at a medical intensive care unit of a University-affiliated hospital, were enrolled in this study. Sixteen patients were treated according to the paraquat poisoning treatment guidelines and 12 received an intravenous infusion of deferoxamine in addition to the treatment guidelines. Results: There were no differences between the two groups in terms of age, gender, severity of paraquat poisoning, and the time elapsed from ingestion to presentation at hospital. There was no difference in overall mortality between the two groups but the incidence of respiratory failure in the deferoxamine group was higher than in the conventional group(4/7 versus 0/9, p=0.019). Conclusion: Deferoxamine seems to have no clinical benefit compared with the conventional treatment. (Tuberc Respir Dis 2007; 62: 113-118)

배양림프구에서 Paraquat의 세포독성에 대한 Vitamin C와 Deferoxamine의 항산화 효과

어은경,김경희,Eo Eun-Kyung,Kim Kyung-Hee 대한임상독성학회 2006 대한임상독성학회지 Vol.4 No.1

Purpose: As basic information of antioxidant treatments for the patient with paraquat intoxication, in human peripheral lymphocytes, the cytotoxicity of paraquat was measured, and to evaluate the antioxidant effect of vitamin C and deferoxamine against this cytotoxicity, malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured. Methods: From 10 healthy adults, after obtaining a consent, 20ml peripheral blood was collected. Experimental groups were divided to (1) control group, the group treated with an identical amount of saline, (2) P group: the group treated with paraquat only, (3) PV group: the group treated with paraquat followed by vitamin C 30 minutes later, (4) PD group: the group treated with paraquat followed by deferoxamine 30 minutes later, (5) PVD group: the group treated with paraquat followed by vitamin C 30 minutes later and subsequently deferoxamine one hour later, and (6) PDV group: the group treated with paraquat followed by deferoxamine 30 minutes later and subsequently vitamin C 1 hour later, and thus to total 6 groups. In each group, 10 samples of peripheral blood was assigned and $100{\mu}M\;paraquat,\;100{\mu}M$ vitamin C, and $100{\mu}M$ deferoxamine were used as reagent. Lymphocytes were isolated, cultured, and cytotoxicity was measured by the Microculture Tetrazolium method (MTT assay), MDA and SOD activity, and TAS concentration were measured. Results: In regard to the cytotoxicity measured in each group, their cytotoxicity was decreased in the group treated with antioxidants, in comparison with the group treated with paraquat only. In the cases that the order of the treatment of these two antioxidants was altered, viability in the PDV group $(1.077{\pm}0.121)$ was increased more that the PVD group $(0.888{\pm}0.152)$ statistically significantly (p=0.018). Concerning the amount of MDA, in comparison with the P group $(6.78{\pm}0.93{\mu}mol/L)$, after the treatment of each antioxidant, the concentration of MDA was decreased statistically significantly (p<0.05). In the group treated with two antioxidants together, in comparison with the group treated only with one antioxidant, the amount of MDA was increased statistically significantly $(PV:\;3.96{\pm}0.98{\mu}mol/L,\;PD:\;4.92{\pm}1.50{\mu}mol/L,\;PVD:\;3.22{\pm}0.83{\mu}mol/L,\;and\;PDV:\;3.42{\pm}0.95{\mu}mol/L,\;p=0.007)$. The concentration of SOD measured in the blood in each group after the administration of paraquat, in comparison with the control group, a pattern of the elevation of SOD activity and subsequent decrease was detected, however, it was not statistically significant. In the comparison of the groups treated with antioxidants, in comparison with the P group $(1419.9{\pm}265.9{\mu}mol/L)$, SOD activity was decreased statistically significantly in only the PDV group $(1176.4{\pm}238.9{\mu}mol/L)$ (p=0.017). In regard to TAS measured in each group, in comparison with the P group $(0.87{\pm}0.05{\mu}mol/L)$, in all groups treated with the antioxidants, the PV group was $1.00{\pm}0.03{\mu}mol/L$ (p=0.005), the PD group was $9.01{\pm}0.24{\mu}mol/L$ was $4.64{\pm}3.98{\mu}mol/L$ (P=0.005), and the PDV group was $9.41{\pm}0.27{\mu}mol/La$ (p=0.005), and thus total antioxidant activity was increased statistically significantly In a multiple comparison test, the PDV group showed the highest total antioxidant activity (p<0.0001). Conclusion: The result of the assessment of the antioxidant effect of vitamin C and deferoxamine on paraquat-induced cytotoxicity showed that in regard to cytotoxicity, SOD activity and TAS measurement, the best result was observed in the PDV group. Therefore, it was found that vitamin C and deferoxamine were effective antioxidants for the paraquat-induced cytotoxicity, and it suggests that the administration of deferoxamine fol

수혈의존성 헤모시데린침착증 치료제의 투여경로 변화에 따른 경제성 평가: 주사제와 경구제의 비교

김진현,김윤희 대한혈액학회 2008 Blood Research Vol.43 No.2

Background: Patients with transfusional iron overload have relied on treatment with deferoxamine, a standard chelating agent. Deferoxamine is administered by intravenous or subcutaneous infusion over an 8∼12 hour period 5∼7 times per week; however, administration of deferoxamine may lead to poor compliance and reduced quality of life in patients. The use of deferasirox, a once daily oral chelation agent, was recently approved. We conducted an economic evaluation of these two iron-chelating medications in transfusion-dependent patients. Methods: The efficacy of oral deferasirox and infusion deferoxamine was assumed equal based on clinical trials of non-inferiority with the administration of 20mg/kg/day deferasirox versus 40mg/kg/day deferoxamine. Depending on the methods utilized for measuring administration time, travel time and convenience between the use of infusion and oral therapy, either cost analysis or cost-utility analysis was undertaken, respectively. Cost analysis included determination of direct medical costs (drug costs and administration costs), non-medical costs (travel costs), and indirect costs (productivity loss associated medical utilization). For cost utility analysis, the cost per QALYs (quality-adjusted life years) was calculated based on costs subtracting indirect costs (productivity loss) and gains of QALYs between the two agents. Results: Deferasirox therapy resulted in a cost savings per patient of 23,471,777 Korean won based on cost analysis. Based on cost utility analysis, the cost per QALYs gained was −398,576 Korean won (4,527,819 Korean won savings with a gain of 11.5 QALYs per patient). Conclusion: The results of cost analysis and cost utility analysis of the use of oral deferasirox versus infusion deferoxamine showed that deferasirox is a more economical and potentially socially beneficial iron-chelating agent in Korea.

心臟 再灌流損傷에 대한 Deferoxamine의 心筋保護 硏究

남충희,이길로 순천향대학교 1994 논문집 Vol.17 No.2

When ischemically stored heart transplants are reperfused (reoxygenated), iron catalysis is involved in the generation of the highly cytotoxic hydroxyl radical and in the chain reactions of subsequent lipid peroxidation that lead to irreversible membrane damage. In 30 isolated working rabbit hearts, I assessed the effects of the iron chelator deferoxamine which might have protective effect on myocardium by blocking of iron catalysis. The experimental procedures are as followings; After non-working retrograde perfusion (15 min.), the perfusion sytem was converted to working mode(15 min.) and heart rate, peak aortic pressure, aortic flow, and coronary flow were obtained at the end. The hearts were arrested with St. Thomas' cardoplegic solution II(4˚C, 3 min.) and stored in the same solution for 2 hrs(the last myocardial temperature; 2˚C). At the end of cold storage, the hearts were perfused with the same solution(4˚C ~ 18˚C) which intended to simulate the implantation procedure of heart. After reperfusion cardioplegia with the same solution(28˚C, 3 min., CPK leakage checked) and non-working retrograde reperfusion(15 min., CPK leakage for initial 3 min.), working perfusion(15 min.) was done and post-ischemic cardiodynamics were measured at the end. After all procedures, biopsy for electron microscopy was done from LV septum(2 randomly selected for each group) and wet and dry weights of the hearts were measured for tissue water and water content. Control group(15) was done as the above procedures, but in the experimental group(15), deferoxamine was mixed into reperfusion cardioplegia(0.04 mMol/L) and reperfusion Krebs-Henseleit solution(0.01 mMol/L). No significant difference between the 2 groups was found on heart rate, peak aortic pressure, and coronary flow but the percent recovery of aortic flow(control; 52.64 ± 1.89 % vs experimental; 62.66 ± 3.24 %, p=0.0124), cardiac output(control; 54.35 ± 1.97 % vs experimental; 65.15 ±3.30 %, p=0.0089), and stroke volume(control; 61.82 ± 2.32 % vs experimental; 69.41 ± 2.89 %, p=0.05) were significantly better in the experimental group. No significant difference between the 2 groups was found in the tissue water(control; 5.36 ± 0.14 vs experimental; 5.15 ± 0.30gm/dry gm of heart) and water content(control; 84.18 ±0.35 % vs experimental; 83.23 ±0.76 %). The leakage of CPK was significantly lowered in the experimental group on the reperfusion cardioplegia(control; 97.48 ± 12.67 vs experimental; 28.45 ± 4.59IU/L/dry gm of heart, p<0.0001) and inital reperfusion(control;44.31 ±6.92 vs experimental; 17.19 ±3.74 IU/L/dry gm of heart, p=0.0018). The myocardium of the experimental group was preserved better than the control group in the electron microgram finding. Conclusively, this study revealed that deferoxamine added to the reperfusion cardioplegia and reperfusion buffer reduce significantly the reperfusion injury presumably by chelation of iron catalysis after cold storage and global ischemia in the isolated working rabbit hearts.

흰쥐에서 Deferoxamine이 신 허혈 후 재관류에 의해 유발되는 신손상에 미치는 영향

배인수,정희창,박동춘 大韓泌尿器科學會 1998 Korean Journal of Urology Vol.39 No.7

뇌경색후 Lipid Peroxidation에 미치는 Allopurinol 및 Deferoxamine의 효과에 대한 실험적 연구

권택현,박윤관,정용구,정흥섭,서중근,이훈갑,주정화,이기찬 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.1

It has been hypothesized that ischemia, followed by reperfusion, facilitates peroxidative free radical chain process in brain. This study was undertaken to investigate the effect of allopurinol and deferoxamine on cerebral lipid peroxidation, estimated by a thiobarbituric acid test, following transient bilateral forebrain ischemia in the rat model of four vessel occlusion. Sprague-Dawley rats fed ad libitum were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 48 hours later temporarily occluding the common carotid arteries for 20minutes. Carotid artery blood flow was restored and rats were decapitated after 48 hours. We assessed the lipid peroxidation capacity of cerebral homogenates obtained from hippocampus, basal ganglia, cortex and thalamus. The homogenates were subjected to 30 minutes of aerobic incubation. The production of lipid peroxides were decreased in all sampled area in the treated groups compared with the control group. Allopurinol and deferoxamine-treated groups showed decreased lipid peroxide levels in all the sampled area, but especially more in the hippocampus, (p=0.02), (p<0.01) repecxtively. Combined group (allopurinol and deferoxamine) showed decreased lipid peroxide levels in all the sampled area, but was not statistcally significant(p>0.05). The results suggest that allopurinol and deferoxamine play a role in protecting ischemic cellular damages by scavenging free radicals and subsequently lipid peroxides formed by oxygen supply through blood reperfusion.

Deferoxamine과 Deferasirox에 의한 면역반응 비교

정대철,정영숙,배이영,정낙균,조빈,김학기,민창기,한치화,김호식 대한혈액학회 2008 Blood Research Vol.43 No.3

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. (Korean J Hematol 2008;43:150-158.)