Interleukin 18 (IL-18) as a target for immune intervention.

Wawrocki, Sebastian; Druszczyńska, Magdalena; Kowalewicz-Kulbat, Magdalena; Rudnicka, Wiesława

doi:10.18388/abp.2015_1153

Cited by 122 publications

(93 citation statements)

References 33 publications

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“…Monocytes can differentially secrete IL-18 or IL-1β, in response to specific signaling, such as leptin (20). Further, while IL-1β activation is tightly regulated by the inflammasome (19), IL-18 can be activated by non-canonical pathways (caspase-3 and Fas-induced caspase-8) and is regulated by the endogenous inhibitor, IL-18BP (6, 28, 38). Thus, IL-18 may represent a common signal downstream of different inflammatory pathways, and may occasionally function independent of IL-1β activity.…”

Section: Discussionmentioning

confidence: 99%

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure

Butts

Butler

Dunbar

et al. 2017

Medicine &Amp; Science in Sports &Amp; Exercise

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Background Aerobic capacity, as measured by peak oxygen uptake (V̇O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1β and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF. The purpose of this study is to examine the relationships between ASC methylation, IL-1β, and IL-18 with peak V̇O2 in persons with HF. Methods This study examined the relationship between ASC methylation, IL-1β, and IL-18 with peak V̇O2 in 54 stable outpatients with HF. All participants were NYHA class II or III, not engaged in an exercise program, and physically able to complete an exercise treadmill test. Results Mean peak V̇O2 was 16.68 ± 4.7 ml/kg/min. Peak V̇O2was positively associated with mean percent ASC methylation (r=.47, p=.001) and negatively associated with IL-1β (r=-.38, p=.007). Multiple linear regression models demonstrated that peak V̇O2 increased by 2.30 ml/kg/min for every 1% increase in ASC methylation and decreased by 1.91 ml/kg/min for every 1 pg/mL increase in plasma IL-1β. Conclusions Mean percent ASC methylation and plasma IL-1β levels are associated with clinically meaningful differences in peak V̇O2 in persons with HF. Inflammasome activation may play a mechanistic role in determining aerobic capacity. ASC methylation is a potentially modifiable mechanism for reducing the inflammatory response, thereby improving aerobic capacity in HF.

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Section: Discussionmentioning

confidence: 99%

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure

Butts

Butler

Dunbar

et al. 2017

Medicine &Amp; Science in Sports &Amp; Exercise

View full text Add to dashboard Cite

show abstract

“…Circulating levels and biological activity depends on the level of production of IL-18, its natural inhibitory protein IL-18BP (IL-18 binding protein) as well as the surface expression of IL-18 receptors (IL-18R) on responding cells (23). Thus, variation in the levels of IL-18 might be determined by polymorphisms regulating the expression of these genes or as yet unidentified genes that encode for the proteins that interact with IL-18.…”

Section: Discussionmentioning

confidence: 99%

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

et al. 2017

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Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines, including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. 1538 participants with active HIV and/or HCV infection in 3 ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with logIL-18 including HCV and HIV infection status and HIV-RNA, in each ancestry group and then meta-analyzed. Eleven highly correlated SNPs (r2=0.98-1) in the IL18-BCO2 region were significantly associated with logIL-18; Each T allele of rs80011693 confers a decrease of 0.06 log pg/mL of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=-0.06, P-value=2.7×10-4). In conclusion, genetic variation in IL18 is associated with IL-18 production in response to HIV and HCV infection and may explain variability in the inflammatory outcomes of chronic viral infections.

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“…Steatosis which is believed to be initiated by IR is considered as the first hit, while changes in cytokines and oxidative stress are considered as the second hit, resulting in disease progression 6. Cytokines are produced by T helper cells, which are categorized as T helper 1 cells, secreting pro-inflammatory cytokines such as interleukin (IL)-18,7 and T helper 2 cells, secreting anti-inflammatory cytokines such as IL-10 8. Several lines of evidence support a role for IL-18 in the pathogenesis of IR and NAFLD,6 while only a few studies have examined the role of IL-10 in NAFLD pathogenesis 3.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease

Borai¹,

Shaker²,

Kamal³

et al. 2017

Journal of Clinical and Translational Hepatology

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Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a silent disease; its spectrum includes simple steatosis, nonalcoholic steatohepatitis and fibrosis. Pro- and anti-inflammatory cytokines play roles in the pathogenesis of NAFLD and insulin resistance (IR). Moreover, plasma cell antigen-1 (PC-1) is related to IR and associated with NAFLD progression. Therefore, we aimed to detect biomarkers, ultrasonographic and anthropometric findings capable of differentiating NAFLD grades, since most previous investigators were concerned more with NAFLD patients without classifying them into grades.Methods: A total of 87 NAFLD patients (31 with grade 1 (mild NAFLD), 26 with grade 2 (moderate NAFLD) and 30 with grade 3 (severe NAFLD) were included in the study, in addition to 47 controls (grade 0). All subjects underwent ultrasonographic examination for NAFLD diagnosis. Serum interleukin-10 (IL-10), plasma interleukin-18 (IL-18) and plasma PC-1 levels were determined using enzyme-linked immunosorbent assay.Results: Homoeostasis model assessment (HOMA)-IR was higher in different NAFLD grades than in controls. Ultrasonographic and anthropometric findings and lipid profile indices (except for high-density lipoprotein cholesterol, which was decreased) were increased with NAFLD progression. Grade 3 patients showed significant increase in levels of IL-18 and significant decrease in IL-10 and PC-1 levels when compared to grade 1 patients.Conclusion: Anthropometric and ultrasonographic findings were valuable in differentiating NAFLD grades. IR is very important in NAFLD pathogenesis. IL-18, HOMA-index and PC-1 levels could be used to differentiate between NAFLD grades, together with other measurements.

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Interleukin 18 (IL-18) as a target for immune intervention.

Cited by 122 publications

References 33 publications

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease

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