Destruction of Rat Islet Cell Monolayers by Cytokines: Synergistic Interactions of Interferon-γ, Tumor Necrosis Factor, Lymphotoxin, and Interleukin 1
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TLDR
Results indicate that the cytokine products of mononuclear cells of the immune system, IFN-γ, TNF, LT, and IL-1 have strong synergistic cytotoxic effects on islet cells and therefore may act as direct chemical mediators of islet β-cell destruction in type I (insulin-dependent) diabetes.Abstract:
An assay was developed to detect the cytotoxic effects of cytokines on rat pancreatic islet cells in monolayer culture. Cell lysis was detected by a 51Cr-release assay after 4 days of incubation with various cytokines. When tested alone, murine (rat and mouse) interferon-gamma (mIFN-gamma) produced a small dose-dependent lysis of islet cells; human IFN-gamma, mouse IFN-alpha/beta, interleukins 1 and 2 (IL-1 and IL-2), tumor necrosis factor (TNF), and lymphotoxin (LT) were inactive. When added together, the following combinations of cytokines showed synergistic cytotoxic effects: TNF (or LT) plus IL-1, TNF (or LT) plus mIFN-gamma, and IL-1 plus mIFN-gamma. These results indicate that the cytokine products of mononuclear cells of the immune system, IFN-gamma, TNF, LT, and IL-1 have strong synergistic cytotoxic effects on islet cells and therefore may act as direct chemical mediators of islet beta-cell destruction in type I (insulin-dependent) diabetes.read more
Citations
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References
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Susumu Makino,Kikuko Kunimoto,Yoshihiro Muraoka,Yukio Mizushima,Ken Katagiri,Yoshihiro Tochino +5 more
TL;DR: The nod mouse may be a useful animal model for investigating the human juvenile type diabetes because of the high frequency of lymphocyte infiltration around and/or into the Langerhans' islet.
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Pathologic Anatomy of the Pancreas in Juvenile Diabetes Mellitus
TL;DR: Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease, and may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on theinsular tissue.
Journal ArticleDOI
Immune interferon: a pleiotropic lymphokine with multiple effects.
Giorgio Trinchieri,Bice Perussia +1 more
TL;DR: Some aspects of the biology of IFN-γ, its pleiomorphic anti-cellular effects and its ability to modulate cellular responses to other regulatory factors are discussed.
Journal ArticleDOI
Human tumor necrosis factor produced by human B-cell lines: synergistic cytotoxic interaction with human interferon
TL;DR: Comparative studies with human alpha, beta, and gamma interferons indicated that sensitivity to hTNF and interferon can be distinguished, and combined treatment with hT NF and alpha or gamma interFERon resulted in a synergistic cytotoxic effect.
Journal ArticleDOI
HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin.
Ricardo Pujol-Borrell,I Todd,M Doshi,G F Bottazzo,Robert Sutton,Derek W. R. Gray,G R Adolf,Marc Feldmann +7 more
TL;DR: It is reported here that IFN-γ in combination with either TNF or LT induces islet cell class II expression, which has important implications for the pathogenesis of type I diabetes and the understanding of the differential control of class IIexpression.