Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives

Kreiner, Frederik Flindt; Kraaijenhof, Jordan M; Herrath, Matthias von; Hovingh, G. Kees; Scholten, Bernt Johan von

doi:10.1080/1744666x.2022.2045952

Cited by 43 publications

(21 citation statements)

References 130 publications

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“…Insufficient remodeling of the spiral arteries are thought to be important, in addition to different immunological factors that are believed to play a significant role in development of preeclampsia 22 . Diabetes type 1 and 2, chronic kidney disease and rheumatoid arthritis are all immunological diseases, and a common feature is their increased levels of pro‐inflammatory interleukin‐6 in affected individuals 23 . Elevated levels of interleukin‐6 are also seen in people with high BMI 24 and might explain the increase in predicted proportions when BMI exceeds 23.…”

Section: Discussionmentioning

confidence: 99%

Pregestational maternal risk factors for preterm and term preeclampsia: A population‐based cohort study

Sande

Dalen

Torkildsen

et al. 2023

Acta Obstet Gynecol Scand

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IntroductionMost studies on factors affecting the risk of preeclampsia have not separated preterm from term preeclampsia, and we still know little about whether the predisposing conditions have a differentiated effect on the risk of preterm and term preeclampsia. Our aim was to assess whether diabetes type 1 and 2, chronic kidney disease, asthma, epilepsy, rheumatoid arthritis and chronic hypertension were differentially associated with preterm and term preeclampsia.Material and methodsThis is a nationwide, population‐based cohort study containing all births registered in the Medical Birth Registry of Norway from 1999 to 2016. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRRs) with 95% confidence intervals (95% CIs), adjusting for maternal age, parity, multiple gestation and all other studied maternal risk factors.ResultsWe registered 1 044 860 deliveries, of which 9533 (0.9%) women had preterm preeclampsia (<37 weeks) and 26 504 (2.5%) women had term preeclampsia (>37 weeks). Most of the assessed maternal risk factors were associated with increased risk for both preterm and term preeclampsia, with adjusted RRRs ranging from 1.2 to 10.5 (preterm vs no preeclampsia) and 0.9–5.7 (term vs no preeclampsia). Diabetes type 1 and 2 (RRR preterm vs term preeclampsia 2.89, 95% CI 2.46–3.39 and RRR 1.68, 95% CI 1.25–2.25, respectively), chronic kidney disease (RRR 1.55, 95% CI 1.11–2.17) and chronic hypertension (RRR 1.85, 95% CI 1.63–2.10) were more strongly associated with preterm than term preeclampsia in adjusted analyses. For asthma, epilepsy and rheumatoid arthritis, RRRs were closer to one and not significant when comparing risk of preterm and term preeclampsia. Main results were similar when using a diagnosis at <34 weeks to define preterm preeclampsia.ConclusionsDiabetes type 1 and 2, chronic kidney disease and chronic hypertension were more strongly associated with preterm than term preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Pregestational maternal risk factors for preterm and term preeclampsia: A population‐based cohort study

Sande

Dalen

Torkildsen

et al. 2023

Acta Obstet Gynecol Scand

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“…TNF-α in turn leads to NF-κB activation [ 50 ] [via c-Jun N-terminal kinases and IκB kinase ( 42 )] and translocation to the nucleus, which propagates further inflammatory responses. IL-1 inhibits β-cell function, and IL-6 translocation to the liver results in the production of the inflammatory biomarker C-reactive protein, which is strongly associated with T2D and cardiometabolic health [ 51 ]. Of note, increases in LPS have been linked to decreases in Bifidobacterium spp, among others [ 52 ], whereas supplementing diets with specific probiotics including Lactobacillus, Bifidobacterium, Clostridium, and Akkermansia have been shown to reduce inflammatory responses and increase insulin sensitivity [ 53 , 54 ], reinforcing the central role, and potential therapeutic implications, of gut microbes in T2D.…”

Section: Mechanisms By Which Gut Microbes Influence Glucose Metabolis...mentioning

confidence: 99%

Type 2 Diabetes and the Microbiome

Mathur

2022

Journal of the Endocrine Society

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Diabetes represents one of the most significant, and rapidly escalating, global health care crises we face today. Diabetes already affects one tenth of the world’s adults, more than 537 million people, numbers which have already tripled since 2000 and which are estimated to reach 643 million by 2030. Type 2 diabetes (T2D), the most prevalent form, is a complex disease with numerous contributing factors, including genetics, epigenetics, diet, lifestyle, medication use, and socioeconomic factors. In addition, the gut microbiome has emerged as a significant potential contributing factor in T2D development and progression. Gut microbes and their metabolites strongly influence host metabolism and immune function, and are now known to contribute to vitamin biosynthesis, gut hormone production, satiety, maintenance of gut barrier integrity and protection against pathogens, as well as digestion and nutrient absorption. In turn, gut microbes are influenced by diet and lifestyle factors such as alcohol and medication use, including antibiotic use and the consumption of probiotics and prebiotics. Here, we review current evidence regarding changes in microbial populations in T2D, and the mechanisms by which gut microbes influence glucose metabolism and insulin resistance, including inflammation, gut permeability, and bile acid production. We also explore the interrelationships between gut microbes and different T2D medications and other interventions, including prebiotics, probiotics and bariatric surgery. Lastly, we explore the particular role of the small bowel in digestion and metabolism, and the importance of studying small bowel microbes directly in our search to find metabolically-relevant biomarkers and therapeutic targets for T2D.

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“…Furthermore, higher circulating levels of IL-6 are associated with poor outcomes and higher mortality in patients with later stages of CKD [ 26 , 27 ]. Interestingly, it is still unknown if the increased levels of IL-6 constitute a pathogenic trigger or a manifestation of, for example, reduced renal clearance of the cytokine due to the lowered glomerular filtration function associated with renal dysfunction [ 28 ]. Additionally, it is worth mentioning that the signaling response of tubular epithelial cells to pro-fibrotic cytokines, such as TGFβ, might be boosted by IL-6.…”

Section: Inflammationmentioning

confidence: 99%

“…Based on the inflammatory mechanism of CKD development, we can distinguish two medications that directly target IL-6 ligand and block classical signaling and trans-signaling; they are called sirukumab and siltuximab. In addition, there are antibodies such as tocilizumab and sarilumab whose role is blocking all three types of IL-6 signaling ( Table 3 ) [ 28 ]. Another antibody was described by Hsu et al [ 93 ].…”

Section: New Targets Of Treatmentmentioning

confidence: 99%

New Insights into Molecular Mechanisms of Chronic Kidney Disease

et al. 2022

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Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms of its underlying causes. In our paper, we discuss the molecular mechanisms of the development and progression of CKD, focusing on oxidative stress, the role of the immune system, neutrophil gelatinase-associated lipocalin, and matrix metalloproteinases. Moreover, growing evidence shows the importance of the role of the gut–kidney axis in the maintenance of normal homeostasis and of the dysregulation of this axis in CKD. Further, we discuss the therapeutic potential and highlight the future research directions for the therapeutic targeting of CKD. However, additional investigation is crucial to improve our knowledge of CKD progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

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Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives

Cited by 43 publications

References 130 publications

Pregestational maternal risk factors for preterm and term preeclampsia: A population‐based cohort study

Pregestational maternal risk factors for preterm and term preeclampsia: A population‐based cohort study

Type 2 Diabetes and the Microbiome

New Insights into Molecular Mechanisms of Chronic Kidney Disease

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