Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans
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Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. / Bendtzen, K; Mandrup-Poulsen, T; Nerup, J; Dinarello, C A; Svenson, M; Nielsen, Jens Høiriis.
I: Science (New York, N.Y.), Bind 232, Nr. 4757, 20.06.1986, s. 1545-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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TY - JOUR
T1 - Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans
AU - Bendtzen, K
AU - Mandrup-Poulsen, T
AU - Nerup, J
AU - Dinarello, C A
AU - Svenson, M
AU - Nielsen, Jens Høiriis
PY - 1986/6/20
Y1 - 1986/6/20
N2 - Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This cytotoxic activity was eliminated from crude cytokine preparations by adsorption with immobilized, purified antibody to interleukin-1 (IL-1). The islet-inhibitory activity and the IL-1 activity (determined by its comitogenic effect on thymocytes) were recovered by acid wash. Purified natural IL-1 and recombinant IL-1 derived from the predominant pI 7 form of human IL-1, consistently inhibited the insulin response. The pI 6 and pI 5 forms of natural IL-1 were ineffective. Natural and recombinant IL-1 exhibited similar dose responses in their islet-inhibitory effect and their thymocyte-stimulatory activity. Concentrations of IL-1 that inhibited islet activity were in the picomolar range. Hence, monocyte-derived pI 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin-dependent diabetes mellitus.
AB - Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This cytotoxic activity was eliminated from crude cytokine preparations by adsorption with immobilized, purified antibody to interleukin-1 (IL-1). The islet-inhibitory activity and the IL-1 activity (determined by its comitogenic effect on thymocytes) were recovered by acid wash. Purified natural IL-1 and recombinant IL-1 derived from the predominant pI 7 form of human IL-1, consistently inhibited the insulin response. The pI 6 and pI 5 forms of natural IL-1 were ineffective. Natural and recombinant IL-1 exhibited similar dose responses in their islet-inhibitory effect and their thymocyte-stimulatory activity. Concentrations of IL-1 that inhibited islet activity were in the picomolar range. Hence, monocyte-derived pI 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin-dependent diabetes mellitus.
KW - Animals
KW - Cell Survival
KW - Glucagon
KW - Humans
KW - Insulin
KW - Interferon-gamma
KW - Interleukin-1
KW - Islets of Langerhans
KW - Monocytes
KW - Rats
KW - Recombinant Proteins
KW - T-Lymphocytes
M3 - Journal article
C2 - 3086977
VL - 232
SP - 1545
EP - 1547
JO - Science
JF - Science
SN - 0036-8075
IS - 4757
ER -
ID: 47975012