Serum Cytokine and Vitamin Levels in Experimental Diabetic Rats

Yazar, Mete; Değer, Yeter; Yur, Fatmagül

doi:10.3923/javaa.2011.622.626

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…However, despite the results obtained with anakinra, we could not detect any increase in the circulating concentrations of both cytokines after two weeks evolution of diabetes. This is in agreement with previous results determining IL-1β in this model [ 62 ], although increased serum levels of TNF-α have been detected in high fat fed/streptozotocin-induced type 2 diabetic rats [ 63 ]. Indeed, an enhancement in the plasmatic IL-1β or TNF-α concentrations is even hardly detected in diabetic patients [ 64 - 66 ].…”

Section: Discussionsupporting

confidence: 93%

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats

Vallejo

Palacios

Romacho

et al. 2014

Cardiovasc Diabetol

103

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BackgroundEndothelial dysfunction is a crucial early phenomenon in vascular diseases linked to diabetes mellitus and associated to enhanced oxidative stress. There is increasing evidence about the role for pro-inflammatory cytokines, like interleukin-1β (IL-1β), in developing diabetic vasculopathy. We aimed to determine the possible involvement of this cytokine in the development of diabetic endothelial dysfunction, analysing whether anakinra, an antagonist of IL-1 receptors, could reduce this endothelial alteration by interfering with pro-oxidant and pro-inflammatory pathways into the vascular wall.ResultsIn control and two weeks evolution streptozotocin-induced diabetic rats, either untreated or receiving anakinra, vascular reactivity and NADPH oxidase activity were measured, respectively, in isolated rings and homogenates from mesenteric microvessels, while nuclear factor (NF)-κB activation was determined in aortas. Plasma levels of IL-1β and tumor necrosis factor (TNF)-α were measured by ELISA. In isolated mesenteric microvessels from control rats, two hours incubation with IL-1β (1 to 10 ng/mL) produced a concentration-dependent impairment of endothelium-dependent relaxations, which were mediated by enhanced NADPH oxidase activity via IL-1 receptors. In diabetic rats treated with anakinra (100 or 160 mg/Kg/day for 3 or 7 days before sacrifice) a partial improvement of diabetic endothelial dysfunction occurred, together with a reduction of vascular NADPH oxidase and NF-κB activation. Endothelial dysfunction in diabetic animals was also associated to higher activities of the pro-inflammatory enzymes cyclooxygenase (COX) and the inducible isoform of nitric oxide synthase (iNOS), which were markedly reduced after anakinra treatment. Circulating IL-1β and TNF-α levels did not change in diabetic rats, but they were lowered by anakinra treatment.ConclusionsIn this short-term model of type 1 diabetes, endothelial dysfunction is associated to an IL-1 receptor-mediated activation of vascular NADPH oxidase and NF-κB, as well as to vascular inflammation. Moreover, endothelial dysfunction, vascular oxidative stress and inflammation were reduced after anakinra treatment. Whether this mechanism can be extrapolated to a chronic situation or whether it may apply to diabetic patients remain to be established. However, it may provide new insights to further investigate the therapeutic use of IL-1 receptor antagonists to obtain vascular benefits in patients with diabetes mellitus and/or atherosclerosis.

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Section: Discussionsupporting

confidence: 93%

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats

Vallejo

Palacios

Romacho

et al. 2014

Cardiovasc Diabetol

103

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“…The animals receiving the drug exhibited a clear improvement of endothelium-dependent relaxations that was paralleled by the normalization of NADPH oxidase activity in the vascular wall ( Vallejo et al, 2014 ). Intriguingly, the circulating levels of IL-1β were not found to be enhanced ( Vallejo et al, 2014 ), as previously reported by others in experimental models ( Yazar et al, 2011 ) or in diabetic patients ( Mooradian et al, 1991 ; Pereira et al, 2014 ). The local over-expression of IL-1β in the vascular wall may be responsible for a paracrine inflammatory response, similarly to that described in vitreous samples from patients with proliferative diabetic retinopathy ( Patel et al, 2008 ).…”

Section: Il-1β Blockade and Experimental Diabetic Vasculopathysupporting

confidence: 84%

IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus

et al. 2017

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Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. In this context, the pharmacological approaches to treat diabetes should not only correct hyperglycaemia, but also attenuate inflammation and prevent the development of metabolic and cardiovascular complications. Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. The drugs currently used in clinical practice are anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, the soluble decoy receptor rilonacept and the monoclonal antibodies canakinumab and gevokizumab. This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients.

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“…It is further suggested that the major part of IL-2 is to maintain immune tolerance by promoting Treg cell development, functional fitness and stability in T1D (d 'Hennezel, Konete, & Piccirillo, 2010). Recently, it has been found that serum IL-2 levels significantly decreased in experimental diabetic rats, indicating that this cytokine plays a role in the pathogenesis of diabetes mellitus (Yazar, Degar, & Yur, 2011). IFN-c is typically secreted by infiltrating immune cells in insulitis in T1D.…”

Section: Discussionmentioning

confidence: 99%

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide protects the spleen and liver from spontaneous inflammation in non-obese diabetic mice by modulating pro-/anti-inflammatory cytokine gene expression

Liao

Lin

2011

Food Chemistry

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Serum Cytokine and Vitamin Levels in Experimental Diabetic Rats

Cited by 5 publications

References 7 publications

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats

IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide protects the spleen and liver from spontaneous inflammation in non-obese diabetic mice by modulating pro-/anti-inflammatory cytokine gene expression

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