Effects Of Low-grade Inflammation Research Articles

Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (β [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

The effects of low-grade inflammation and sleep loss on model-based and model-free control: Results of an experimental double hit model

The effects of low-grade inflammation and sleep loss on model-based and model-free control: Results of an experimental double hit model

Abstract MP13: Evaluation Of The Effect Of Low Grade Inflammation And Hypertension On The Development Of White Matter Lesions

Introduction: The risk of degenerative disease development is closely linked to persistent and continuous systemic inflammation. Although relationships between chronic low-grade inflammation (LGI) measurements and the progression of cardiovascular diseases are becoming established, the burden of the cardio-pathology and LGI on the central nervous system has not been fully investigated. Specifically, there is limited data on how hypertension (HTN) and related LGI impact white matter lesion (WML) pathogenesis. Methods: We examined 448 subjects with a mean age of 69.3 ± 7.4 years, with 62% of the cohort being women (n=276), and 45% having hypertension (n=200). Components of the LGI score included white blood cell count, albumin levels, platelet counts, and granulocyte/lymphocyte ratio, modified after. Larger LGI scores represented an increase in measured LGI intensity at that time point. MR images were obtained on a 3T system using fluid attenuation inversion recovery (FLAIR) sequence. WML burden was ascertained using Fazekas scale, done separately for both deep WML and periventricular WML. Summated score of greater than or equal to 4 was considered high overall WML burden. Results: It was found that subjects with hypertension had significantly higher LGI score when compared to subjects without hypertension after accounting for sex and BMI (F=4.8, p=0.03). Using logistic regression. we found that LGI score was related to higher WML burden (p=0.047) within the entire cohort. However, further analyses have shown that this finding was driven by the normotensive group, in which the relationship between higher WML burden and respective LGI score was significant (p=0.007). This was not the case among hypertensive subjects. Conclusion: It is clear from the data presented that a relationship between LGI and hypertension exists, confirming that inflammation is an underlying process in cardiovascular pathogenesis. However, LGI scores were related to WML in only normotensive cohorts. We offer that the effects of chronic HTN (related to higher inflammatory score itself ) overshadow the effect of LGI among hypertensive subjects. It is worth emphasizing that even in subjects without HTN white matter damage is related to LGI

Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner

In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclear localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β3-integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β3-integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis.

Low-grade inflammation is associated with lower haemoglobin levels in healthy individuals: results from the Danish blood donor study.

Chronic inflammation can lead to anaemia of chronic disease due to the sequestration of iron caused by inflammatory cytokines and the protein hepcidin. However, the effect of low-grade inflammation (LGI) on haemoglobin among healthy individuals is not known. This study examines the effect of LGI on haemoglobin among Danish blood donors. We performed multivariable linear regression to assess the effect of LGI (i.e. high-sensitivity C-reactive protein above 3 mg/l but below 10 mg/l) on haemoglobin in 17 322 Danish blood donors. We also performed multivariable logistic regression to evaluate the effect of LGI on the risk of having low haemoglobin (below the 10th percentile among men and women, respectively). We adjusted for donation activity, age, sex, low ferritin, oral contraceptives and menopause. All analyses were stratified by current smoking status. LGI was associated with lower haemoglobin (0·08 mm lower [0·12 g/dl], 95% confidence interval (CI): -0·11-0·05) and increased risk of low haemoglobin (OR = 1·22, 95% CI: 1·05-1·43) in non-smokers. Conversely, LGI was associated with higher haemoglobin in smokers (0·12 mm [0·19 g/dl], 95% CI: 0·06-0·18). In this first study of LGI and haemoglobin in healthy individuals, there was a negative association between LGI and haemoglobin in non-smokers. The association was positive in smokers, probably because smoking leads to both increased inflammation and increased haemoglobin through CO exposure.

Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population?

ObjectiveFibroblast growth factor 23 (FGF23) is a phosphaturic agent involved in calcium–phosphate homeostasis. Recent findings show that iron deficiency and inflammation regulate FGF23 release and/or biodegradation. Iron deficiency is frequently observed in the elderly, therefore the aim of this study was to find out if iron deficiency is independent from low grade inflammatory factors affecting both forms of FGF23 that are detectable in circulation in a large population-based study of elderly subjects. Design and methodsThe analysis included 3780 elderly (1798 females) PolSenior study participants and assessed levels of phosphorus, calcium, iron, ferritin, interleukin 6, C-reactive protein (hs-CRP), intact (iFGF23), and c-terminal FGF (cFGF23). The analysis was performed for all subjects and terciles of serum iron levels in relation to hs-CRP were calculated. ResultsThe highest plasma cFGF23 and iFGF23 concentrations were found in subjects with the lowest serum iron levels (p<0.001). The effect of low grade inflammation was markedly weaker and affected only iFGF23 levels. The adjusted serum levels of hs-CRP, iPTH, phosphorus, and 25-(OH)-D3 analysis revealed that plasma iFGF23 and cFGF23 levels were almost unchanged up to a serum iron level of 59.3ng/mL and 57.3ng/mL respectively and then were nearly linearly increasing by 0.285pg/mL and 3.742RU/mL for each unit of serum iron increase. ConclusionsLow iron levels are associated with increased levels of both cFGF23 and iFGF23, independent of low grade inflammation. A similar analysis of cFGF23 and iFGF23 does not suggest enhanced biodegradation of iFGF23 induced by iron deficiency.

Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: Evidence for inter-generational effects of low grade inflammation

Background: Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown.Aim: To evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women.Subjects and methods: Data come from 234 parous Filipino females (21.5 ± 0.3 years) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), tumour necrosis factor alpha (TNFα), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW.Results: BW in female offspring was lower only among women with high IL-1β. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p < 0.104) gave birth to the largest males.Conclusion: Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential inter-generational effects of chronic low-grade inflammation.

Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: Evidence for inter-generational effects of low grade inflammation

Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: Evidence for inter-generational effects of low grade inflammation

Circulating Heat Shock Protein 70 in Health, Aging and Disease

BackgroundHeat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.ResultsSerum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.ConclusionsThe present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.

Effects of low-grade inflammation on arterial stiffness and wave reflections in hypertensive patients with metabolic syndrome

Effects of low-grade inflammation on arterial stiffness and wave reflections in hypertensive patients with metabolic syndrome

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors

The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.