title: Successful islet transplantation to two recipients from a single donor by targeting proinflammatory cytokines in mice.
abstract: BACKGROUND
  Currently, the inability to achieve successful islet transplantation from one donor to one recipient is a major obstacle facing clinical islet transplantation. We herein determined whether this limitation could be overcome by targeting pro-inflammatory cytokines with the prevention of immediate islet graft loss in association with engraftment in mice.
  
  
  METHODS
  Isolated islets were grafted into the liver of streptozotocin-induced diabetic mice and the role of proinflammatory cytokines in the engraftment of islets was evaluated with the use of interferon (IFN)-gamma-/- mice and monoclonal antibodies against proinflammatory cytokines.
  
  
  RESULTS
  Hyperglycemia in streptozotocin-induced diabetic mice receiving 200 syngenic islets, which were isolated from a single mouse pancreas, was ameliorated when IFN-gamma-/-, but not wild-type mice, were used as recipients. The treatment with anti-IFN-gamma antibody produced normoglycemia in diabetic wild-type mice receiving 200, but not 100 islets. However, when anti-tumor necrosis factor-alpha and anti-interleukin-1beta antibodies were administered in conjunction with anti-IFN-gamma antibody, wild-type diabetic mice receiving 100 islets became normoglycemic after transplantation. In addition, the favorable effect of the combined use of antibodies was similarly achieved in mice receiving islet allografts when rejection was prevented with anti-CD4 antibody treatment.
  
  
  CONCLUSIONS
  These findings clearly demonstrate that successful islet transplantation from one donor to two recipients is feasible by targeting pro-inflammatory cytokines in mice, thus suggesting a potential application in clinical islet transplantation if similar mechanisms of islet graft loss could be mediated in humans.
authors: Department of Surgery, Fukuoka University, Fukuoka, Japan.
authors: Masayuki
authors: M
authors: Satoh
authors: Yohichi
authors: Y
authors: Yasunami
authors: Nobuhide
authors: N
authors: Matsuoka
authors: Masahiko
authors: M
authors: Nakano
authors: Takeshi
authors: T
authors: Itoh
authors: Tomoyuki
authors: T
authors: Nitta
authors: Keizo
authors: K
authors: Anzai
authors: Junko
authors: J
authors: Ono
authors: Masaru
authors: M
authors: Taniguchi
authors: Seiyo
authors: S
authors: Ikeda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005947:Glucose; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013311:Streptozocin / Q000494:pharmacology; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D013311:Streptozocin; D005947:Glucose