Summary
Following activation peritoneal macrophages from diabetes prone BB rats secreted strikingly higher amounts of tumour necrosis factor alpha than found for macrophages from diabetes resistant or normal Wistar rats. Enhanced tumour necrosis factor alpha production was detected prior to the occurrence of insulitis. Cultures of macrophages derived from precursor cells in diabetes prone BB rat bone marrow also showed upregulated tumour necrosis factor alpha secretion upon challenge with endotoxin and interferon gamma. Tumour necrosis factor alpha hypersecretion may contribute to autoimmune diabetes by affecting thymic and post-thymic T-cell maturation and by promoting pancreatic islet inflammation.
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Hanenberg H, Kolb-Bachofen V, Kantwerk-Funke G, Kolb H (1989) Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of prediabetic BB rats. Diabetologia 32: 126–134
Appels B, Burkart V, Kantwerk-Funke G, Funda J, Kolb-Bachofen V, Kolb H (1989) Spontaneous cytotoxicity of macrophages against pancreatic islet cells. J Immunol 142: 3803–3808
Mandrup-Poulsen T, Bendtzen K, Nerup J, Dinarello CA, Svenson M, Nielson JH (1986) Affinity-purified human Interleukin-I is cytotoxic to isolated islets of Langerhans. Diabetologia 29: 63–67
Pukel C, Baquerizo H, Rabinovitch A (1988) Destruction of rat islet cell monolayers by cytokines: synergistic interactions of Interferon-gamma, Tumour Necrosis Factor, Lymphotoxin and Interleukin I. Diabetes 37: 133–136
Unglaub R, Maxeiner B, Thoma B, Pfizenmeier K, Scheurich P (1987) Downregulation of Tumour Necrosis Factor sensitivity via modulation of TNF binding capacity by protein kinase C activators. J Exp Med 166: 1788–1797
Buchan G, Barrett K, Turner M, Chantry D, Maini RN, Feldmann M (1988) Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL1α. Clin Exp Immunol 73: 449–455
Jacob CO, McDevitt HO (1988) Tumour necrosis factor-α in murine autoimmune ‘Lupus’ nephritis. Nature 331: 356–358
Satoh J, Seino H, Abo T, Tanaka S, Shintani S, Ohta S, Tamura K, Sawai T, Nobunaga T, Oteki T, Kumagai K, Toyota T (1989) Recombinant human tumour necrosis factor α suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84: 1345–1348
Bendtzen K, Morling N, Fomsgaard A, Svenson M, Jakobsen B, Odum N, Svejgaard A (1988) Association between HLA-DR 2 and production of tumour necrosis factor α and interleukin 1 by mononucleated cells activated by lipopolysaccharide. Scan J Immunol 28: 599–606
Molvig J, Worsaa H, Wogensen L, Bach L, Nielsen LS, Nerup J (1989) Monocyte functions in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 32: 518A
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Rothe, H., Fehsel, K. & Kolb, H. Tumour necrosis factor alpha production is upregulated in diabetes prone BB rats. Diabetologia 33, 573–575 (1990). https://doi.org/10.1007/BF00404147
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DOI: https://doi.org/10.1007/BF00404147