Iron Deficiency Increases Early Inflammatory Allo-lmmune Responses After Liver Transplantation in Rats, But Does Not Impair the Establishment of Spontaneous Tolerance.

Bonaccorsi Riani, Eliano;Danger, Richard;Kodela, Elisavet;Miquel, Rosa;Sanchez-Fueyo, Alberto;et.al.
(2015) 21st International Liver Transplantation Society (ILTS) Annual International Congress — Location: Chicago, USA (8.July.2015)

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Authors
  • Bonaccorsi Riani, ElianoUCLouvain
    Author
  • Danger, Richard
    Author
  • Kodela, Elisavet
    Author
  • Miquel, Rosa
    Author
  • Sanchez-Fueyo, Alberto
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Abstract
(en) The prediction of success of immunosuppression (IS) withdrawal (operational tolerance) in clinical liver transplantation is related with differential expression of iron homeostasis genes (e.g. HAMP, TFRC) suggesting that the iron/hepcidin axis may influence the establishment of tolerance. To study the influence of iron status in the establishment of tolerance in liver transplantation, we set up an experimental model of arterialized rat liver transplantation using a syngeneic (Lewis-Lewis), spontaneous tolerant (Brown Norway-Lewis) and Tacrolimus induced tolerant (Dark Agouti-Lewis) rat strain combinations, in which donors and recipients were fed with an iron-deficient (Ir Def; <3mg/kg) or iron-balanced diet (Ir Repl; carbonyl iron: 200mg/Kg) during three weeks (donors) and one week (recipients) before the transplant and kept under the same diet regimen after transplantation. Iron deficient diet regimen did not influence body weight and liver function tests, but significantly reduced intra-hepatic and serum iron levels comparing with the iron replete diet regimen. All strain combination groups had the same clinical outcome with similar liver function tests evolution in the early days post-transplant in both diets. When Spontaneous tolerant rats were challenged with Recombinant human IL-2 (200.000IU/ day) during the first three weeks post-transplant, Ir-Def animals presented significantly clinical deterioration when compared with Ir-Repl animals (15% weight lost, p=0.001) followed by impairment of the liver function tests during the time (ALT p=0.01; AST p=0.03, BIL p=0.025. This was associated with more intra-hepatic CD4+ T cells (p=0.04) and less CD8+ T cells (p=ns), more ischemic lesions and cytokine production (IfnG) in Ir- Def animals (p=ns). When the experiment was replicated using syngeneic transplant animals (Lewis-Lewis), no alteration were observed neither in Ir-Repl nor in Ir-Def animals. These results suggest that iron deficiency exacerbates the early post-transplant liver injury in the spontaneous tolerant rat model, but only when the system is challenged with exogenous IL-2.
Affiliations
  • King's College London, UKInstitue of liver studies

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Bonaccorsi Riani, E., Danger, R., Kodela, E., Miquel, R., Martinez-Llordella, M., Hernandez-Fuentes, M., & Sanchez-Fueyo, A. (2015). Iron Deficiency Increases Early Inflammatory Allo-lmmune Responses After Liver Transplantation in Rats, But Does Not Impair the Establishment of Spontaneous Tolerance. Transplantation, 99(7 Suppl. 1), 193. https://hdl.handle.net/2078.5/64347 (Original work published 2015)