title: Interferon-gamma sensitizes rat pancreatic islet cells to lysis by cytokines and cytotoxic cells.
abstract: Immunoregulatory polypeptides (cytokines) produced by mononuclear cells of the immune system can inhibit insulin secretion and may be cytotoxic to pancreatic islet beta cells. We used a modified 51Cr release cytotoxicity assay to define the interactive cytotoxic effects of interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon gamma (IFN-gamma) on rat islet cells in monolayer culture. We here demonstrate that (a) IFN-gamma, but not IL-1 or TNF, can sensitize islet cells to subsequent cytolysis by other cytokines (IL-1 or TNF); (b) the cytolytic effect of sequential addition of IFN-gamma, then IL-1 or TNF (approximately 35-40% 51Cr release) is similar to that produced by the concurrent addition of IFN-gamma plus IL-1 or TNF; (c) the priming effect of IFN-gamma persists for 3 to 6 or more days after its removal; and (d) islet cells preincubated with IFN-gamma are also more sensitive to cytolysis by splenic mononuclear cells from diabetes-prone BB/Wor rats. These findings suggest that IFN-gamma produced by activated T lymphocytes and monocytic cells infiltrating islets in Type 1 diabetes may play a direct and important role in sensitizing beta cells to damage by other cytokines (IL-1, TNF) and cytotoxic cells in the immune/inflammatory infiltrate.
authors.affiliation: Department of Medicine, Muttart Diabetes Research and Training Centre, Edmonton, Alberta, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Baquerizo
authors.forename: A
authors.initials: A
authors.lastname: Rabinovitch
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology*; D051381:Rats; D011913:Rats, Inbred BB; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007371:Interferon-gamma