Effector mechanisms in low-dose streptozotocin-induced diabetes.
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.
Immunology Unit, Faculty of Medicine, UAE University, Al Ain, United Arab Emirates.
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ML
Lukić
S
S
Stosić-Grujicić
A
A
Shahin
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D013311:Streptozocin
D007375:Interleukin-1; D009569:Nitric Oxide; D013311:Streptozocin; D007371:Interferon-gamma