In T2D, IL-18 and IL-1RA were positively associated with depression for two scores (IL-18: PHQ-9, WHO-5; IL-1RA: CES-D, WHO-5), hsCRP was associated with one depression score (PHQ-9), and adiponectin showed an inverse association with one depression score (PHQ-9) after adjustment (P = 0.006-0.048).
Genotype A/A of IL-18 gene promoter -607 C/A polymorphism was associated with higher prevalence of type 2 diabetes and 2 h post-loading plasma glucose level.
IL-18 levels were significantly higher in men as compared to women, and in patients with diabetes type 2 and metabolic syndrome compared to those without (p ≤ 0.001, all).
Our results indicate that T2DM aggravates HF after MI through defective mitophagy, associated exaggerated inflammasome activation, cell death, and IL-18 secretion, suggesting that restoring mitophagy and inhibiting inflammasome activation may serve as novel targets for the prevention and treatment of HF in T2DM.
In the T2DM + CAS group, the expression levels of the three inflammasome genes and IL-18 were increased in patients with thickened IMT compared to those with the plaque.
Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders.
Patients with CP and uncontrolled T2D presented severe periodontal disease and inflammation (PPD, p = 0.0072; CAL, p = 0.0480; bone loss, p = 0.0088), higher levels of CASP1 mRNA expression (p = 0.0026), a stronger pattern of staining for NLRP3 and ASC proteins in the epithelium and connective tissues, and significantly higher production of IL-18 (p = 0.0063) and IL-1β (p = 0.0018) in comparison with healthy or CP subjects.
The results based on the IVW method demonstrate that high IL-18 plasma levels significantly increase the risk of T2DM, and no heterogeneity or pleiotropic effects appeared after the sensitivity and MR-Egger analyses.
Type 2 diabetes is also a chronic inflammatory condition that leads to inflammasome activation and the release of proinflammatory mediators, including interleukins (ILs) IL-1β and IL-18.
The aim of this study was to evaluate association between G(-137)C polymorphism (rs187238) in the IL-18 gene and risk of diabetes and CVD in type 2 diabetes patients.
Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001).
Therefore, variation within IL18, previously shown to be associated with lower IL18 levels, is influencing measures of obesity both in men with type 2 diabetes mellitus and those with advanced coronary heart disease.
O-BN-based diet does not affect postprandial cytokine levels in health, whereas it renders decreased circulating IL-18 levels along with metabolic biomarkers in T2DM, with no beneficial effect on NfL.
The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a multimeric protein complex that mediates maturation of the cytokines IL-1β and IL-18 as well as release of the proinflammatory protein high-mobility group box 1 (HMGB1) and contributes to several inflammatory diseases, including sepsis, gout, and type 2 diabetes.
CONCLUSIONS IL-18 levels were positively correlated with atherosclerotic burden in patients with T2DM and it may be considered as a significant therapeutic target.
The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99-1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09-1.21] per 0.28 SD increase in IL-18 levels).
The evolutive advantages of increased inflammatory responses, hypersecretion of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-18], or decreased anti-inflammatory molecules (adiponectin, certain TNF-alpha isoforms, soluble CD14, etc.), would lead in westernized countries to chronic inflammation conditions, such as obesity and type 2 diabetes, resulting in cardiovascular disease.
The IL-18 serum level was higher in T2D and LADA than that in control subjects, but did not differ between both diabetic groups, even when they were BMI matched.
Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes.
Recently, an anti-IL18 monoclonal antibody, which decreased free IL18 levels, was found to be safe, yet ineffective in a phase II trial for type 2 diabetes.
This finding supports the concepts that adipocytes behave as primitive immune cells and that IL-18 may mediate some of the detrimental complications of obesity such as cardiovascular disease and type 2 diabetes.
We performed immmunohistochemical analysis of IL-18 and IL-18 receptor (IL-18 R) in human kidney tissue derived from 12 subjects with type 2 diabetes and overt nephropathy, and compared with those in 7 subjects with minimal change nephrotic syndrome (MCNS).