Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness

Yong, Kenneth; Ooi, Esther M.M.; Dogra, Gursharan; Mannion, Morgan; Boudville, Neil; Chan, Doris; Lim, Ee Mun; Lim, Wai H.

doi:10.1016/j.cyto.2013.05.023

Cited by 25 publications

(26 citation statements)

References 15 publications

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“…Systemic concentrations of pro-/anti-inflammatory cytokines are several times higher in individuals with CKD, which is the result of decreased renal clearance and increased production [31]. Certain cytokines (such as IL-12 and IL-18), which are implicated in immune inflammation, are also known to be active in the development of CKD [32,33]. This situation leads to the disruption of the cells and tissues and it has deleterious effects on the body.…”

Section: Discussionmentioning

confidence: 99%

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

et al. 2017

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ObjectiveIncreased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE).MethodsThis was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1–5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival.ResultsIL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000).ConclusionThis is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients.

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Section: Discussionmentioning

confidence: 99%

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

et al. 2017

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“…Interleukins are extensively studied biomarkers of inflammation in CVD and the plasma levels of many interleukins, IL 6, IL-12, IL-18 among them, have been shown to be elevated in later stages of CKD [7, 35]. IL-6 levels predict the risk of developing incident CKD [8] as well as CVD and mortality in patients with end-stage renal disease [36].…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4

Weber

Duchateau‐Nguyen

Solier

et al. 2014

Clinical Kidney Journal

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BackgroundThe contribution of pro-inflammatory markers to cardiovascular (CV) risk and vascular calcification in chronic kidney disease (CKD) remains largely to be elucidated. We investigated the association between plasma levels of several biomarkers and calcification volume in three different vascular beds in CKD Stages 3 and 4 patients.MethodsThis is a cross-sectional, exploratory study in patients with an estimated glomerular filtration rate (eGFR) ≥20 and ≤45 mL/min/1.73 m2 and serum phosphorus ≥3.5 and <6.0 mg/dL enrolled in a previously published randomized, double blind, placebo-controlled single-centre trial. Ethylenediaminetetraacetic acid (EDTA) plasma samples were collected at baseline before patients received study medication and analysed for the presence of a number of biomarkers. Coronary artery calcium (CAC), thoracic aortic calcification (TAC) and abdominal aortic calcification (AAC) volumes were measured using standard electron-beam computed tomography protocols. Associations were adjusted for age, sex, smoking, body mass index, diabetes mellitus status, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and eGFR.ResultsAssociations with CAC were found for β2-microglobulin (B2M), fibroblast growth factor 23 (FGF23), interleukin-8 (IL-8) and IL-18. AAC was associated with: B2M, FGF23 and IL-2 receptor alpha (IL-2 RA). TAC was associated with: B2M, FGF23, IL-2 RA, IL-18 and tumour necrosis factor receptor type I. For most of the analysed biomarkers, there were non-significant trends of associations with calcification.ConclusionsThis exploratory study found that elevated plasma levels of several inflammatory biomarkers are significantly associated with arterial calcification in CKD Stages 3 and 4 patients. A greater understanding of inflammation and calcification in CKD patients may help the development of CV risk-assessment algorithms for better management of these patients.

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“…Upregulated IL12 has been found in various inflammatory conditions, including sarcoidosis (Shigehara et al , ), coronary artery disease (Wegner et al , ), periodontitis (Robati et al , ), chronic liver failure (Liu et al , ), cardiovascular diseases and atherosclerosis (Weyand & Goronzy, ; Yong et al , ,b; Nikolajuk et al , ). It is also upregulated in type 2 diabetes (T2D) (Gverović et al , ); in particular, T2D individuals with higher insulin resistance and abnormal lipids exhibit elevated IL12, endothelial dysfunction and proinflammatory markers (Mishra et al , ).…”

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confidence: 99%

Interleukin‐12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): the lesser known side of inflammation

2017

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SummaryInflammation, with its associated inflammatory molecules, is integral to most chronic diseases, including the various cardiovascular diseases. Interleukin 12 (IL12) is one of the inflammatory cytokines that is upregulated during inflammation; however, we know very little about its exact effect on red blood cells (RBCs), platelets and fibrin(ogen). IL12 is an important pleiotropic cytokine in early inflammatory responses and has potent immunomodulatory, antitumour and anti-infection activity. Here we investigate how low levels of circulating IL12, comparable to levels found during chronic inflammation, affect coagulation parameters, platelets and RBCs. We used thromboelastography, scanning electron microscopy, refractometery and wide-field microscopy. Our results show that IL12 caused hypercoagulation, platelet activation and spreading, as well as RBC agglutination. This phenomenon has far-reaching implications for treatment of the plethora of conditions where IL12 is upregulated, since it suggests aberrant haemorheology as agglutination affects blood flow. This information might be used in future to target the lowering of IL12 in inflammatory conditions, as well as address RBC agglutination.

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Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness

Cited by 25 publications

References 15 publications

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4

Interleukin‐12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): the lesser known side of inflammation

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