title: Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes.
abstract: OBJECTIVE
  Research on the pathogenesis of type 1 diabetes relies heavily on good animal models. The aim of this work was to study the translational value of animal models of type 1 diabetes to the human situation.
  
  
  METHODS
  We compared the four major animal models of spontaneous type 1 diabetes, namely the NOD mouse, BioBreeding (BB) rat, Komeda rat and LEW.1AR1-iddm rat, by examining the immunohistochemistry and in situ RT-PCR of immune cell infiltrate and cytokine pattern in pancreatic islets, and by comparing findings with human data.
  
  
  RESULTS
  After type 1 diabetes manifestation CD8(+) T cells, CD68(+) macrophages and CD4(+) T cells were observed as the main immune cell types with declining frequency, in infiltrated islets of all diabetic pancreases. IL-1β and TNF-α were the main proinflammatory cytokines in the immune cell infiltrate in NOD mice, BB rats and LEW.1AR1-iddm rats, as well as in humans. The Komeda rat was the exception, with IFN-γ and TNF-α being the main cytokines. In addition, IL-17 and IL-6 and the anti-inflammatory cytokines IL-4, IL-10 and IL-13 were found in some infiltrating immune cells. Apoptotic as well as proliferating beta cells were observed in infiltrated islets. In healthy pancreases no proinflammatory cytokine expression was observed.
  
  
  CONCLUSIONS
  With the exception of the Komeda rat, the animal models mirror very well the situation in humans with type 1 diabetes. Thus animal models of type 1 diabetes can provide meaningful information on the disease processes in the pancreas of patients with type 1 diabetes.
authors: Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany.
authors: Anne
authors: A
authors: Jörns
authors: Tanja
authors: T
authors: Arndt
authors: Andreas
authors: A
authors: Meyer zu Vilsendorf
authors: Jürgen
authors: J
authors: Klempnauer
authors: Dirk
authors: D
authors: Wedekind
authors: Hans-Jürgen
authors: HJ
authors: Hedrich
authors: Lorella
authors: L
authors: Marselli
authors: Piero
authors: P
authors: Marchetti
authors: Nagakatsu
authors: N
authors: Harada
authors: Yutaka
authors: Y
authors: Nakaya
authors: Gen-Sheng
authors: GS
authors: Wang
authors: Fraser W
authors: FW
authors: Scott
authors: Conny
authors: C
authors: Gysemans
authors: Chantal
authors: C
authors: Mathieu
authors: Sigurd
authors: S
authors: Lenzen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D011913:Rats, Inbred BB; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma