title: HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R Antibody in Mice.
abstract: OBJECTIVE
  The limited success in achieving insulin independence of patients with type 1 diabetes mellitus after islet transplantation from a single donor, mainly due to early loss of transplanted islets, hampers clinical application of islet transplantation. Previously, we have shown in mice that the early loss of transplanted islets in the liver, the site of islet transplantation, is caused by innate immune rejection triggered by high-mobility group box 1 (HMGB1) protein released from transplanted islets. We herein determined whether the HMGB1-mediated early loss of transplanted mouse islets is prevented by anti-interleukin-6 receptor (IL-6R) antibody.
  
  
  METHODS
  The effect of anti-IL-6R antibody on amelioration of hyperglycemia in streptozocin-induced diabetic mice receiving 200 islets into the liver from a single donor was evaluated in association with HMGB1-stimulated interferon-γ production of hepatic mononuclear cells.
  
  
  RESULTS
  Hyperglycemia of diabetic mice receiving 200 syngeneic islets was ameliorated with down-regulation of interferon-γ production of hepatic natural killer T cells and neutrophils when anti-IL-6R was administered at the time of transplantation. This beneficial effect was also seen in allografts when alloimmune rejection was prevented by anti-CD4 antibody.
  
  
  CONCLUSIONS
  These findings demonstrate that anti-IL-6R antibody prevented the early loss of intrahepatic islet grafts with inhibiting HMGB1-induced immune activation after islet transplantation.
authors: From the *Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University; and †Murakami Karindo Hospital, Fukuoka, Japan.
authors: Takeshi
authors: T
authors: Itoh
authors: Tomoyuki
authors: T
authors: Nitta
authors: Hitomi
authors: H
authors: Nishinakamura
authors: Daibo
authors: D
authors: Kojima
authors: Toshiyuki
authors: T
authors: Mera
authors: Junko
authors: J
authors: Ono
authors: Shohta
authors: S
authors: Kodama
authors: Yohichi
authors: Y
authors: Yasunami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000601:surgery*; D006085:Graft Survival / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D019947:Receptors, Interleukin-6; D007371:Interferon-gamma