title: Rapid increase of interleukin-10 plasma levels after combined auxiliary liver-kidney transplantation in presensitized patients.
abstract: BACKGROUND
  After transplantation, donor dendritic cells (DCs) in the grafted organ are activated by an ischemia/reperfusion-induced inflammatory process that induces their migration to the recipient's secondary lymphoid tissues. The subsequent interaction between migrated and mature donor DCs, recipient T cells, and natural killer (NK) cells is proposed to be crucial in directing host immune reactions toward allograft rejection. A liver transplant is less prone to induce rejection compared with most other solid organ transplants, and simultaneous transplantation of liver and kidney is known to improve the clinical outcome of kidney transplantation.
  
  
  RESULTS
  Here we show that liver as well as combined auxiliary liver-kidney transplantation in patients induces a rapid increase in plasma interleukin-10 (IL-10) to levels that are significantly higher than those seen after standard kidney transplantation. Addition of IL-10 during in vitro maturation of human monocyte-derived DCs with ischemia/reperfusion-associated factors was found to affect phenotypic DC maturation significantly. Addition of IL-10 inhibited DC production of the NK cell- and T cell-recruiting chemokines CXCL9, CXCL10 and CXCL11.
  
  
  CONCLUSIONS
  Our findings indicate that liver transplantation induces a substantial systemic release of IL-10, which may inhibit T cell- and NK cell-mediated rejection processes toward the transplanted liver and concurrently transplanted kidney.
authors.affiliation: 1 Department of Infectious Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 2 Department of Immunology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 3 Department of Surgery, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 4 Department of Clinical and Molecular Medicine (Nephrology), Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 5 Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden. 6 Department of Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 7 Address correspondence to: Jenny Nyström, Ph.D., Gothenburg University, Institute of Neuroscience and Physiology, Renal Physiology, P. O. Box 432, 40530 Gothenburg, Sweden.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Ingelsten
authors.forename: Karin
authors.initials: K
authors.lastname: Gustafsson
authors.forename: Michael
authors.initials: M
authors.lastname: Olausson
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.forename: Alex
authors.initials: A
authors.lastname: Karlsson-Parra
authors.forename: Jenny
authors.initials: J
authors.lastname: Nyström
mesh_terms: D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood*; D053583:Interleukin-1beta / Q000378:metabolism; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology; D016031:Liver Transplantation; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C508609:IL10 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma