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.
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).
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.
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.
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).
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.
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 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.
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.
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 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.
Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders.
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).
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.
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.
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).
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).
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.
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.
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.