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Mechanism of immune tolerance induced by Immutol combined with CsA in rat cardiac transplantation
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  • Jun Ma,
  • Xinxue Zhang,
  • Zhe Liu,
  • Huanye Liu,
  • Long Yang,
  • Jiantao Kou,
  • Xianliang Li,
  • Qiang He
Jun Ma
Beijing Chao-Yang Hospital

Corresponding Author:[email protected]

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Xinxue Zhang
Beijing Chao-Yang Hospital
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Zhe Liu
Beijing Chao-Yang Hospital
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Huanye Liu
Beijing Luhe Hospital
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Long Yang
Beijing Chaoyang Hospital Jingxi Branch
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Jiantao Kou
Beijing Chao-Yang Hospital
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Xianliang Li
Beijing Chao-Yang Hospital
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Qiang He
Beijing Chao-Yang Hospital
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Abstract

Backgrounds: Indoleamine 2,3-dioxygenase (IDO) has previously been elucidated in tolerant cardiac or liver transplantation models. Kynurenine has also been reported in immune tolerant models. Immutol is an analogue of IDO and metabolites, and it is an anthranilic acid derivative and is a synthetic chemical. Its function in tolerant rat cardiac transplantation remains unknown. Here, we elucidated the role and mechanism of Immutol combine with CsA in tolerant cardiac transplantation. Methods: Using a rat cardiac transplantation model intervented by Immutol, CsA, and Immutol+CsA before surgery. Moreover, we used 1-MT, the IDO inhibitory, to furtherly validate the role and the mechanism in the immune tolerance of cardiac transplantation Results: In this study, we show that the combination of Immutol with CsA can alleviate rejection and prolong recipients’ survival compared with that in the Immutol or CsA groups. Moreover, the protein level of Kynurenine was high overexpression in the Immutol+CsA group, and the expression level of IDO and Kynurenine was increased with survival time longer in the Immutol+CsA group. Furthermore, we used 1-MT to detect the role of Immutol in the rat cardiac transplantation. The results revealed that rejection was aggravated, and survival time was shortened after the IDO was successfully blocked. Conclusion: Our data suggest that the combination of Immutol and CsA can alleviate acute rejection and prolongs survival time in a rat cardiac transplantation model; this drug may induce immune tolerance in cardiac transplantation through ‘kynurenine accumulation’, which may provide new ideas and methods for clinical induction of transplant immune tolerance