Combined treatment with interleukin-1 and tumor necrosis factor-alpha antagonists improve type 2 diabetes in rats

Dik, Burak; Bahcivan, Emre; Faki, Hatice Eser; Üney, Kamil

doi:10.1139/cjpp-2017-0769

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…Moreover, inhibiting TNF-α in psoriasis patients with MetS decreased macrophage infiltration and pro-inflammatory cytokines levels in umbilical fat (593). Interestingly, a combined inhibition of IL-1β and TNF-α was more effective in improving IR in T2D rats (594). Similarly targeting IL-6 improved IR and normalized adipokine levels in MetS and fructose-fed rats (595,596).…”

Section: New Avenues For Adipose Tissue Immunomodulation In Metabolicmentioning

confidence: 96%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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Section: New Avenues For Adipose Tissue Immunomodulation In Metabolicmentioning

confidence: 96%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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“…Elevated levels of TNF-α are associated with an increased risk of diabetes and insulin resistance, this can be independent of obesity (34). Additionally, in animal studies, improving insulin resistance with TNF-α antagonist therapy supports the role of TNF-α in the development of T2DM (35). Furthermore, improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation with the blockade of IL-1 with the synthetic IL-1 receptor antagonist anakinra is another strong evidence of the role of pro-inflammatory cytokines in T2DM (36).…”

Section: Discussionmentioning

confidence: 89%

Cytokine Profile in Patients With Maturity-onset Diabetes of the Young (MODY)

DIREN¹,

Demirci

Gül

et al. 2022

In Vivo

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Background/Aim: High-sensitivity C-reactive protein (hs-CRP) is used in the differential diagnosis of maturity-onset diabetes of the young (MODY)-3, but other inflammatory markers have not been investigated in MODY patients. We aimed to compare the serum levels of antiinflammatory and proinflammatory cytokines between MODY patients and healthy subjects and show the inflammatory features in MODY subtypes. Patients and Methods: Thirty patients with clinically suspected MODY and 34 healthy controls were included in this study. Nextgeneration sequencing (NGS) was used for the molecular diagnosis of MODY subtypes. Serum levels of cytokines were measured using a multiplexed cytokine assay and hs-CRP concentration was determined by the immunoturbidimetric assay. Results: The hs-CRP levels were higher in both NGSconfirmed (MODY, n=17) (p=0.009) and n=13) patients (p<0.001) than those in controls. However, , , , , and sCD40L (p=0.007) levels of MODY patients and IL-1β (p=0.002), IL-31 (p<0.001), , and sCD40L (p=0.039) levels of non-MODY patients were lower than those of controls. While hs-CRP levels were lower in MODY3 patients than non-MODY3 patients (p=0.009), IL-17A (p=0.006) and IL-23 (p=0.016) levels for the first time in this study were found to be higher in patients with MODY3 than in patients with other MODY subtypes (p<0. 05). Conclusion: MODY patients had lower serum levels of the proinflammatory cytokines IL-1β, IL-6, TNF-α, IL-31, and sCD40L compared to healthy controls. High IL-17A and IL-23 levels along with low hs-CRP levels may be potential markers to distinguish MODY3 from other MODY subtypes.Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes and comprises about 1-5% of total diabetes (1). The prevalence of MODY has been increasing like other forms of diabetes in Turkey (2). The diagnostic criteria specified in the Practice Guideline for MODY in 2018 are evidence of endogenous insulin secretion, diabetes-onset before the age of 25 in at least one family member, presence of diabetes in two consecutive generations, and absence of autoantibodies to pancreatic islet antigens (1, 3). Mutations in genes responsible for beta cells' development and function cause MODY. To date, different mutations in fourteen genes (HNF4A/MODY1, GCK/MODY2, HNF1A/MODY3, PDX1/MODY4, HNF1B/MODY5, NEUROD1/MODY6, KLF11/ MODY7, CEL/MODY8, PAX4/MODY9, INS/MODY10, BLK/ MODY11, ABCC8/MODY12, KCNJ11/MODY13, and APPL1/ MODY14) have been described as responsible for the pathogenesis of MODY subtypes (3, 4). Recent studies have suggested that some possible biomarkers such as urine and serum amino acids, complement 5 and 8, transthyretin, urine glucose, apolipoprotein M (ApoM), lipid profile, D-glycan index, and cystatin C are useful for the differential diagnosis of 2490

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“…It was thought that it would be better to determine the effect of bidirectional cytokine blockade together with not only histopathological but also other metabolic and molecular markers although the co-administration of anakinra and etanercept did not make a significant difference compared to other treatment groups. Similarly, a study using etanercept and anakinra together reported that it could improve insulin and blood sugar levels in Type 2 diabetic rats and that etanercept was more effective in increasing insulin (Dik et al 2018).…”

Section: Discussionmentioning

confidence: 90%

The effect of etanercept and anakinra on experimental type 2 diabetes pathology in rats

2021

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In this study, the effects of etanercept, anakinra, and their combination on streptozotocin-induced type 2 diabetes in rats were pathologically evaluated. A total of 30 rats were separated into 5 groups as control (C), diabetes (D), diabetes + anakinra (DA), diabetes + etanercept (DE), and diabetes + anakinra + etanercept (DAE). Anakinra (10 mg/kg/day, s.c.) and etanercept (10 mg/kg, twice weekly, s.c.) were administered to the DA and DE groups, respectively, and the DAE group received both anakinra and etanercept for 21 days. Histopathologically, pathological changes related to diabetes in internal organs occurred in the diabetes group, and there was a significant decrease (improvement) in these changes in the treatment groups (P < 0.05). There was no significant difference (P > 0.05) between the treatment groups, but some changes in the liver and kidneys were higher in the combined group which should be taken into account for longer use. Although there was no significant difference, etanercept was more effective on pancreatic lesion scores and anakinra was more effective on testicular changes. As a result, the single or combined use of IL-1 and TNF-α antagonists anakinra and etanercept were effective in the treatment of type 2 diabetes in rats without any toxic-pathological effect.

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Combined treatment with interleukin-1 and tumor necrosis factor-alpha antagonists improve type 2 diabetes in rats

Cited by 12 publications

References 37 publications

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Cytokine Profile in Patients With Maturity-onset Diabetes of the Young (MODY)

The effect of etanercept and anakinra on experimental type 2 diabetes pathology in rats

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