Effector mechanisms in low-dose streptozotocin-induced diabetes

• Published in: Clinical & developmental immunology 1998, Vol.6 (1-2), p.119-128
• Main Authors: Lukić, M L, Stosić-Grujicić, S, Shahin, A
• Format: Article
• Language: English
• Subjects: Animals; Diabetes Mellitus, Experimental - immunology; Insulin-dependent diabetes mellitus; interferon-γ Interferon-gamma - physiology; interleukin- 1; Interleukin-1 - pharmacology; interleukin-1 inhibitor; Islets of Langerhans - pathology; Macrophages - physiology; Mice; nitric oxide; Nitric Oxide - biosynthesis; Rats; RT6+ T cells; Streptozocin; tumor necrosis factor
• ISSN: 1044-6672; 2314-8861; 1740-2522; 2314-7156; 1740-2530
• DOI: 10.1155/1998/92198

The cellular and molecular requirements for beta-cell damages in an immune-mediated toxin-induced insulin-dependent diabetes mellitus have been studied in the model of multiple low-dose streptozotocin-induced diabetes in rats and mice. It was found that strain-related susceptibility to diabetes induction correlated with a higher level of IL-2, IFN-gamma, and TNF-alpha production, whereas such differences were not observed when IL-1 and NO production by macrophages were analyzed; elimination of immunoregulatory RT6+T cells that increases IFN-gamma production, enhances susceptibility to MLD-STZ-induced diabetes; mercury-induced Th-2 cells down-regulated the disease; IFN-gamma-mediated macrophage activation to produce proinflammatory cytokines rather than NO is an important event in early diabetogenic effects of invading macrophages; inhibition of IL-1 activity downregulates diabetes induction; and generation of NO in beta cells appears to be important for diabetogenic effects. Taken together, data indicate that MLD-STZ diabetes induced by Th-1 lymphocytes that secrete soluble effector molecules that activate macrophages and promote destruction of beta cells possibly by both nitric oxide and nonnitric oxide-mediated mechanisms.