IL-13 prolongs allograft survival: Association with inhibition of macrophage cytokine activation

IL-13 prolongs allograft survival: Association with inhibition of macrophage cytokine activation
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DOI:
10.1016/j.trim.2006.09.035
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发表时间:
2007-04-01
影响因子:
1.5
通讯作者:
Hall, Bruce M.
Hall, Bruce M.
中科院分区:
医学4区
文献类型:
--
作者:
Davidson, Cassandra;Verma, Nirupama D.;Hall, Bruce M.

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Th 2细胞因子,特别是IL-4和IL-10,可能促进移植耐受诱导,但另一种Th 2细胞因子IL-13的作用尚不清楚。本研究探讨了大鼠重组IL-13(rIL-13)对同种免疫应答的影响。本文比较了rIL-13在混合淋巴细胞培养(MLC)中对PVG刺激细胞培养的大鼠淋巴细胞的体外作用。用40,000单位的rIL-13处理移植有完全同种异体PVG新生心脏移植物的DA大鼠10天,并通过ECG监测移植物存活。用RT-PCR法检测移植物和淋巴组织中细胞因子mRNA的表达,并检测同种抗体水平。rIL-13对MLC无明显作用,而rIL-4则能促进MLC的增殖,诱导Th 2细胞因子的产生,抑制Th 1细胞因子的产生。rIL-13抑制树突状细胞培养物中IL-12 p35、IL-12 p40和TNF-α mRNA的诱导。rIL-13治疗可使完全同种异体PVG新生儿心脏移植物存活时间延长至18-21(13-27)天(中位数(范围));而未经治疗的正常排斥反应存活时间为12(9-15)天(p
Th2 cytokines, especially IL-4 and IL-10, may facilitate transplant tolerance induction but the role of IL-13, another Th2 cytokine, is not known. This study examined the effects of rat recombinant IL-13 (rIL-13) on alloimmune responses. In vitro effects of rIL-13 were compared in mixed lymphocyte cultures (MLC) on rat lymphocytes cultured with PVG stimulator cells. DA rats grafted with fully allogeneic PVG neonatal heart grafts were treated with 40,000 units of rIL-13 for 10 days and graft survival monitored by ECG. Cytokine mRNA expression in the graft and lymphoid tissues was studied by RT-PCR and alloantibody levels assayed. rIL-13 had no effect on MLC, unlike rIL-4 which enhanced proliferation and induced Th2 and inhibited Th1 cytokines in MLC. rIL-13 inhibited IL-12p35, IL-12p40 and TNF-alpha mRNA induction in dendritie cell cultures. Treatment with rIL-13 prolonged fully allogeneic PVG neonatal heart graft survival to 18-21 (13-27) days (median (range)); compared to 12 (9-15) days in untreated normal rejection (p