Thalidomide attenuates multiple low-dose streptozotocin-induced diabetes in mice by inhibition of proinflammatory cytokines.
Thalidomide is an immunomodulatory and anti-inflammatory agent and is used in autoimmune disorders. It has been shown that thalidomide inhibits proinflammatory cytokines production. The purpose of this study was to investigate the effect of thalidomide on the prevention of autoimmune diabetes in mice. Diabetes was induced by multiple low-dose of streptozotocin (MLDS) injection. Mice were treated with thalidomide (300 mg/kg/day orally) for 21 days. Plasma levels of glucose, insulin and nitrate/nitrite as well as pancreatic cytokine levels were measured. Pathological examinations of the pancreas revealed that thalidomide reduced the islet inflammation (insulitis) and destruction of beta cells. Thalidomide treatment prevented hyperglycemia and preserved pancreatic insulin secretion in the diabetic mice. Thalidomide treatment also significantly decreased plasma levels of nitric oxide and pancreatic proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-12, IL-17 and interferon (IFN)-γ)] while increased anti-inflammatory cytokine IL-10. In conclusion, these findings indicate that thalidomide may have a protective effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.
Department of Pharmacology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. k.amirshahrokhi@arums.ac.ir
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Amirshahrokhi
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Ghazi-Khansari
D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use*
D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D009566:Nitrates; D009573:Nitrites; D013792:Thalidomide