PMID- 25058889
OWN - NLM
STAT- MEDLINE
DCOM- 20161108
LR  - 20161230
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 44
IP  - 1
DP  - 2015 Jan
TI  - HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R 
      Antibody in Mice.
PG  - 166-71
LID - 10.1097/MPA.0000000000000188 [doi]
AB  - OBJECTIVES: 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-gamma production of hepatic mononuclear 
      cells. RESULTS: Hyperglycemia of diabetic mice receiving 200 syngeneic islets was 
      ameliorated with down-regulation of interferon-gamma 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.
FAU - Itoh, Takeshi
AU  - Itoh T
AD  - From the *Department of Regenerative Medicine and Transplantation, Faculty of 
      Medicine, Fukuoka University; and daggerMurakami Karindo Hospital, Fukuoka, Japan.
FAU - Nitta, Tomoyuki
AU  - Nitta T
FAU - Nishinakamura, Hitomi
AU  - Nishinakamura H
FAU - Kojima, Daibo
AU  - Kojima D
FAU - Mera, Toshiyuki
AU  - Mera T
FAU - Ono, Junko
AU  - Ono J
FAU - Kodama, Shohta
AU  - Kodama S
FAU - Yasunami, Yohichi
AU  - Yasunami Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Blood Glucose)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Receptors, Interleukin-6)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/blood/pathology/*surgery
MH  - Diabetes Mellitus, Type 1/blood/pathology/*surgery
MH  - Graft Survival/drug effects
MH  - HMGB1 Protein/*metabolism/pharmacology
MH  - Interferon-gamma/metabolism
MH  - Islets of Langerhans/*drug effects/immunology/metabolism/*surgery
MH  - Islets of Langerhans Transplantation/adverse effects
MH  - Liver/*drug effects/immunology/metabolism/*surgery
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Natural Killer T-Cells/drug effects/immunology/metabolism
MH  - Neutrophils/drug effects/immunology/metabolism
MH  - Receptors, Interleukin-6/*antagonists & inhibitors/metabolism
MH  - Time Factors
EDAT- 2014/07/25 06:00
MHDA- 2016/11/09 06:00
CRDT- 2014/07/25 06:00
PHST- 2014/07/25 06:00 [entrez]
PHST- 2014/07/25 06:00 [pubmed]
PHST- 2016/11/09 06:00 [medline]
AID - 10.1097/MPA.0000000000000188 [doi]
PST - ppublish
SO  - Pancreas. 2015 Jan;44(1):166-71. doi: 10.1097/MPA.0000000000000188.