Low-grade Systemic Inflammation Research Articles

A Chemical Structure and Machine Learning Approach to Assess the Potential Bioactivity of Endogenous Metabolites and Their Association with Early Childhood Systemic Inflammation

Metabolomics has gained much attention due to its potential to reveal molecular disease mechanisms and present viable biomarkers. This work uses a panel of untargeted serum metabolomes from 602 children from the COPSAC2010 mother–child cohort. The annotated part of the metabolome consists of 517 chemical compounds curated using automated procedures. We created a filtering method for the quantified metabolites using predicted quantitative structure–bioactivity relationships for the Tox21 database on nuclear receptors and stress response in cell lines. The metabolites measured in the children’s serums are predicted to affect specific targeted models, known for their significance in inflammation, immune function, and health outcomes. The targets from Tox21 have been used as targets with quantitative structure–activity relationships (QSARs). They were trained for ~7000 structures, saved as models, and then applied to the annotated metabolites to predict their potential bioactivities. The models were selected based on strict accuracy criteria surpassing random effects. After application, 52 metabolites showed potential bioactivity based on structural similarity with known active compounds from the Tox21 set. The filtered compounds were subsequently used and weighted by their bioactive potential to show an association with early childhood hs-CRP levels at six months in a linear model supporting a physiological adverse effect on systemic low-grade inflammation.

High Adherence to the Mediterranean Dietary Pattern Is Inversely Associated with Systemic Inflammation in Older but Not in Younger Brazilian Adults.

The Mediterranean dietary pattern (MPD) has shown promise in preventing low-grade systemic inflammation (LGSI). This study tested if a high adherence to the MDP by younger and older Brazilian adults is associated with lower LGSI and investigated which Mediterranean food components may contribute to these associations. We performed a secondary study on 2015 ISA-Nutrition (290 younger adults (20-59 years old) and 293 older adults (≥60 years old)), a cross-sectional population-based study in São Paulo, SP, Brazil. The adherence to the MDP was assessed using the Mediterranean Diet Score (MedDietScore), obtained from two non-consecutive 24 h dietary recalls (24HDRs). The LGSI score (from plasma CRP, TNF-α, and adiponectin) identified the inflammatory status. Linear regression models assessed the association between LGSI and the MedDietScore. In older adults only, a high adherence to the MDP signified an 11.5% lower LGSI score. Older adults, classified with high adherence to the MDP, differed by consuming lower meat intake and full-fat dairy. Between older adults, the intake of vegetables and olive oil was inversely associated with the levels of LGSI. Thus, among older adults, the intake of some specific Mediterranean food determined high adherence to the MDP and was associated with decreased LGSI.

Adiposity, immunity, and inflammation: interrelationships in health and disease: A report from 24th annual Harvard nutrition obesity symposium, June 2023

The rapidly evolving field of immunometabolism explores how changes in local immune environments may affect the key metabolic and cellular processes, including that of adipose tissue. Importantly, these changes may contribute to low-grade systemic inflammation. In turn, chronic low-grade inflammation affecting adipose tissue may exacerbate the outcome of metabolic diseases. Novel advances in our understanding of immune-metabolic processes may critically lead to interventions to reduce disease severity and progression. An important example in this regard relates to obesity, which has a multifaceted effect on immunity activating the pro-inflammatory pathways such as inflammasome and disrupting cellular homeostasis. This multifaceted effect of obesity can be investigated through study of downstream conditions using cellular and systemic investigative techniques. To further explore this field, the NIH P30 Nutrition Obesity Research Center at Harvard in partnership with the Harvard Medical School assembled experts to present at its 24th annual Symposium entitled “Adiposity, Immunity, and Inflammation: Interrelationships in Health and Disease on June 07, 2023. This manuscript seeks to synthesize and present key findings from the symposium highlighting new research and novel disease-specific advances in the field. Better understanding the interaction between metabolism and immunity offers promising preventative and treatment therapies for obesity-related immunometabolic diseases.

Plasma pentraxin-3 levels and its role in childhood obesity-Is it anti-inflammatory? A matched group study.

Obesity has been associated with chronic low-grade systemic inflammation. This study aimed to investigate the relationship of pentraxin-3 (PTX-3) with anthropometric measurements, dietary content and physical activity level in children. A matched group study. This study was conducted with 91 children aged 6-17 years, divided into two groups: "non-obese group" (Body Mass Index Standard Deviation Score [BMI SDS] <95th percentile) and "obese group" (BMI SDS ≥95th percentile). Plasma PTX-3 levels. The mean age of 91 children included in the study was 12.34 ± 2.86 years. Plasma PTX-3 levels were significantly higher in obese children (p = .028). No significant correlation was found between BMI SDS and plasma PTX-3 values, but a weak positive correlation was found when physical activity level was controlled (r = .176, p = .049). In addition, it was found that fat mass was a partial mediator of plasma PTX-3 level, and an increase in the amount of subcutaneous adipose tissue negatively affected plasma PTX-3 level. Plasma PTX-3 level showed a weak positive correlation (r = .223, p = .017) with physical activity score and dietary polyunsaturated fatty acid intake, while a weak negative correlation with neutrophil-to-lymphocyte ratio. One unit increase in physical activity score or polyunsaturated fatty acid level caused 0.730 and 2.061 unit increases in plasma PTX-3 level, respectively; while one unit increase in dietary fat intake caused 0.413-unit decrease. There was an indirect relationship between the amount of subcutaneous adipose tissue and PTX-3 level. The results of our study suggested that plasma PTX-3 was associated with lower levels of inflammation in children.

Inflammation and weight change related to neurocognitive and functional impairment in diabetes and psychiatric disorders

Introduction: Obesity is a global pandemic associated with various cardio-metabolic and psychiatric disorders. Neurocognitive and functional deficits have been associated with several somatic and psychiatric disorders. Adiposity-related inflammation has recently emerged as a key risk factor for neurocognitive and functional impairments. This prospective transdiagnostic study aimed to investigate the role of adiposity-related inflammatory markers in neurocognitive and functional outcomes associated with weight changes.Methods: Peripheral blood inflammatory and oxidative stress biomarkers and neurocognitive and functional performance were assessed twice over 1 year in 165 individuals, including 30 with schizophrenia, 42 with bipolar disorder, 35 with major depressive disorder, 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls. Participants were stratified by body mass index into categories of type 2 obesity (T2OB; n=30), type 1 obesity (T1OB; n=42), overweight (OW; n=53), and average weight (NW; n=40). Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed.Results: Compared with NW, T2OB and T1OB were significantly associated with impaired neurocognitive and functional performance (p<0.01; η²p=0.06–0.12) and higher levels of C-reactive protein and platelets (PLT) (p<0.01; η²p= 0.08–0.16), with small-to-moderate effect sizes. IL-6, IL-10, and PLT were key factors for detecting significant weight changes in T1OB and T2OB over time. Regression models revealed that inflammatory and oxidative stress biomarkers and cellular adhesion molecules were significantly associated with neurocognitive and functional performance (p<0.05).Discussion: Obesity is characterised by neurocognitive and functional impairments alongside low-grade systemic inflammation. Adiposity-related inflammatory biomarkers may contribute to neurocognitive and functional decline in individuals with T2DM and psychiatric disorders. Our data suggest that these biomarkers facilitate the identification of specific subgroups of individuals at higher risk of developing obesity.

SDIMMMER: A propaedeutic approach in regenerative medicine

SDIMMMER is a proposed acronym for use in medical interviews. It serves as a mnemonic for key areas to focus on during patient assessments. SDIMMMER stands for Sleep, Diet, Microbiome, Metabolism, Medications, Examination, and Rehabilitation. This approach is designed to assist physicians in efficiently evaluating a patient's metabolic profile as a priority and only then implementing suitable interventional regenerative medicine strategies, ensuring precise clinical diagnosis and increased treatment success rates. This acronym represents a pioneering propaedeutic technique in regenerative medicine. The primary goal of SDIMMMER is to monitor the patient's metabolic status and reduce low-grade chronic systemic inflammation, a prominent feature of metabolic syndrome (MS). This inflammatory state is marked by elevated levels of circulating inflammatory cytokines and increased macrophage infiltration in peripheral tissues. The objective of this propaedeutic proposal is to address and treat the patient holistically, enhancing metabolic function and consequently promoting better health of tissues and organ systems. Ultimately, SDIMMMER aims to increase the efficacy of orthobiological treatments by boosting the levels of growth factors, thereby achieving improved outcomes with patients. Beyond specific treatments, the focus is on guiding patients towards positive lifestyle changes, ultimately enhancing overall quality of life and fostering a healthier metabolism.

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Longitudinal association between soft drink consumption and handgrip strength in adults: a prospective analysis from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) cohort study.

Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were -0·70 (-2·49, 1·09) for rarely drinks, -0·82 (-2·62, 0·97) for < 1 cup/week and -0·86 (-2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

Low-grade systemic inflammation stimulates microglial turnover and accelerates the onset of Alzheimer's-like pathology.

Several in vivo studies have shown that systemic inflammation, mimicked by LPS, triggers an inflammatory response in the CNS, driven by microglia, characterized by an increase in inflammatory cytokines and associated sickness behavior. However, most studies induce relatively high systemic inflammation, not directly compared with the more common low-grade inflammatory events experienced in humans during the life course. Using mice, we investigated the effects of low-grade systemic inflammation during an otherwise healthy early life, and how this may precondition the onset and severity of Alzheimer's disease (AD)-like pathology. Our results indicate that low-grade systemic inflammation induces sub-threshold brain inflammation and promotes microglial proliferation driven by the CSF1R pathway, contrary to the effects caused by high systemic inflammation. In addition, repeated systemic challenges with low-grade LPS induce disease-associated microglia. Finally, using an inducible model of AD-like pathology (Line 102 mice), we observed that preconditioning with repeated doses of low-grade systemic inflammation, prior to APP induction, promotes a detrimental effect later in life, leading to an increase in Aβ accumulation and disease-associated microglia. These results support the notion that episodic low-grade systemic inflammation has the potential to influence the onset and severity of age-related neurological disorders, such as AD.

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations

ABSTRACT Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E–7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.

Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

The effect of physical activity on cytokine levels in adults living with type 1 diabetes-a preliminary study.

The aim of this study is to investigate whether physical activity and the level of body fat are factors reducing the level of pro-inflammatory cytokines in people with T1DM. Twenty-five men (27.8 ± 9.4 years old; 178.9 ± 6.9 cm; 80.6 ± 12 kg) and 18 women (28.1 ± 12.5 years old; 162.4 ± 5.5; 63.1 ± 9.9 kg) were divided into four groups based on body fat percentage and level of physical activity (AN-active people with normal body fat; IAN-inactive people with normal body fat; AO-active people with excessive body fat, IAO-inactive people with excessive body fat). The level of cytokines in the blood serum was assessed. The level of IL-8 was higher (measurable) in inactive men, regardless of adiposity degree and in women, only in the inactive group with normal body fat. IL-6 was found only in active men with excessive adiposity. In conclusion, the findings from this study allow to indicate that moderate level of physical activity may contribute to a reduction in the development of systemic low-grade inflammation in patients with T1DM, and thus, may reduce the risk of CVD.

Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18–20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1β was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

The value of neck adipose tissue as a predictor for metabolic risk in health and type 2 diabetes

Upper-body adiposity is adversely associated with metabolic health whereas the opposite is observed for the lower-body. The neck is a unique upper-body fat depot in adult humans, housing thermogenic brown adipose tissue (BAT), which is increasingly recognised to influence whole-body metabolic health. Loss of BAT, concurrent with replacement by white adipose tissue (WAT), may contribute to metabolic disease, and specific accumulation of neck fat is seen in certain conditions accompanied by adverse metabolic consequences. Yet, few studies have investigated the relationships between neck fat mass (NFM) and cardiometabolic risk, and the influence of sex and metabolic status. Typically, neck circumference (NC) is used as a proxy for neck fat, without considering other determinants of NC, including variability in neck lean mass. In this study we develop and validate novel methods to quantify NFM using dual x-ray absorptiometry (DEXA) imaging, and subsequently investigate the associations of NFM with metabolic biomarkers across approximately 7000 subjects from the Oxford BioBank. NFM correlated with systemic insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR), low-grade inflammation (plasma high-sensitivity C-Reactive Protein; hsCRP), and metabolic markers of adipose tissue function (plasma triglycerides and non-esterified fatty acids; NEFA). NFM was higher in men than women, higher in type 2 diabetes mellitus compared with non-diabetes, after adjustment for total body fat, and also associated with overall cardiovascular disease risk (calculated QRISK3 score). This study describes the development of methods for accurate determination of NFM at scale and suggests a specific relationship between NFM and adverse metabolic health.

Could Periodontitis Increase the Risk of Suffering from Pancreatic Cancer?-A Systematic Review.

(1) Background: The relationship between periodontitis and systemic pathologies continues to grow. Recently, the presence of periodontal pathogens has been linked to an increased risk of pancreatic cancer (PC) and its mortality. Thus, a systematic review is needed to identify whether an association between the two diseases can be established. The objective of this review is to elucidate the mechanisms responsible for this association. (2) Methods: A systematic review was carried out using three databases (PubMed, Embase and Scopus) with the following keywords "Periodontitis AND pancreatic cancer". A total of 653 articles were retrieved; before selection and screening, the inclusion and exclusion criteria were defined, resulting in a total of 13 articles being included in the review. (3) Results: The increase in low-grade systemic inflammation, pH changes, and the cytotoxicity of certain periodontopathogenic bacteria were found in the scientific literature reviewed as mechanisms linking periodontitis with the risk of PC. (4) Conclusions: Through this systematic review, we have seen how periodontitis can be related to PC and how it worsens its prognosis. Knowing the behavior of periodontopathogenic bacteria and the influence they have on our immune and inflammatory system may help to achieve an interdisciplinary approach to both pathologies.

Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently.

Inflammation is an important factor contributing to obesity-induced metabolic disorders. Different investigations confirm that local inflammation in adipose issues is the primary reason for such disorder, resulting in low-grade systemic inflammation. Anti-inflammatory, antioxidant, and epigenetic modification are among the varied properties of Quercetin (QCT) as a natural flavonoid. The precise molecular mechanism followed by QCT to alleviate inflammation has been unclear. This study explores whether the anti-inflammatory effects of QCT in 3T3-L1 differentiated adipocytes may rely on SIRT-1. The authors isolated 3T3-L1 pre-adipocyte cells and exposed them to varying concentrations of QCT, lipopolysaccharide (LPS), and a selective inhibitor of silent mating type information regulation 2 homolog 1 (SIRT-1) called EX-527. After determining the optimal dosages of QCT, LPS, and EX-527, they assessed the mRNA expression levels of IL-18, IL-1, IL-6, TNF-α, SIRT-1, and adiponectin using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The study showed considerable cytotoxic effects of LPS (200 ng/mL) + QCT (100 µM) + EX-527 (10 µM) on 3T3-L1 differentiated adipocytes after 48h of incubation. QCT significantly upregulated the expression levels of adiponectin and SIRT-1 (p < 0.0001). However, introducing SIRT-1 inhibitor (p < 0.0001) reversed the impact of QCT on adiponectin expression. Additionally, QCT reduced SIRT-1-dependent pro-inflammatory cytokines in 3T3-L1 differentiated adipocytes (p < 0.0001). This study revealed that QCT treatment reduced crucial pro-inflammatory cytokines levels and increased adiponectin levels following LPS treatment. This finding implies that SIRT-1 may be a crucial factor for the anti-inflammatory activity of QCT.

Association between triglyceride-glucose index and hypertension: a cohort study based on the China Health and Nutrition Survey (2009–2015)

AimInsulin resistance (IR) may participate in the pathogenesis of hypertension by mediating low-grade systemic inflammation. The triglycerides-glucose (TyG) index has recently been suggested as a reliable alternative biochemical marker of IR compared with traditional methods. Herein, we speculated TyG index may also be associated with hypertension.MethodsData of adults were extracted from the China Health and Nutrition Survey (CHNS) in 2009–2015 in this retrospective cohort study. The TyG index was calculated using the formula: TyG = Ln [fasting triglycerides (mg/dL) ×fasting glucose (mg/dL)/2]. Associations between TyG index and hypertension were evaluated by univariate and multivariate logistic regression analyses with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age and gender were also performed. In addition, we assessed the interaction effect between TyG index and body mass index (BMI) on hypertension in participants with different age and gender.ResultsAmong 3,413 eligible participants, 1,627 (47.67%) developed hypertension. The average TyG index in hypertension group and non-hypertension group was 8.58 and 8.39 respectively. After adjusting for covariates, we found that compared with participants with TyG index ≤ 8.41 (median value), those who had higher TyG index seemed to have higher odds of hypertension [OR = 1.17, 95%CI: (1.01–1.37)]. Similarly, this association was also discovered in participants who aged ≤ 65 years old [OR = 1.19, 95%CI: (1.01–1.39)] or were female [OR = 1.35, 95%CI: (1.10–1.65)]. Additionally, there was a potential additive interaction effect between obesity and TyG index on hypertension.ConclusionHigh TyG index was associated with high odds of hypertension in general population in China, but the causal relationship between them needed further exploration.

Lifestyle factors and BMI attenuate relationships between biomarkers of inflammation and depressive symptoms and well-being: A cross-sectional study

BackgroundMental disorders are a growing public health concern and evidence has linked chronic low-grade inflammation with depression and well-being. Research also suggests that certain modifiable lifestyle factors such as smoking, alcohol use, physical activity, diet quality and BMI are related to psychological health. These may modulate the relationship between low-grade inflammation and mental health conditions. In this study we examined inflammatory biomarker associations with two psychological health scores and investigated whether relationships are influenced by lifestyle factors and BMI. MethodsThis was a cross-sectional study of 1824 middle-to older-aged men and women randomly selected from a large primary care centre. Depressive symptoms and well-being were assessed using the 20-item Centre for Epidemiologic Studies Depression (CES-D) Scale and the World Health Organization-Five (WHO-5) Well-Being Index. Linear regression analyses were performed to examine depression and well-being score relationships with six inflammatory biomarkers, and a composite inflammatory biomarker score, adjusting for demographic characteristics, health conditions, lifestyle factors and BMI. ResultsDepression and well-being score associations with complement component 3 (CES-D only) c-reactive protein, interleukin 6, leptin, white blood cell counts, neutrophils and the inflammatory biomarker score were observed. These relationships survived adjustment for demographic variables and health conditions but were attenuated in models which included lifestyle factors and BMI. In final models, only leptin (β = 0.566, p = 0.018) and inflammatory score (β = 0.137, p = 0.004) associations with the CES-D score remained. ConclusionsThese findings suggest that the relationship between systemic low-grade inflammation and depressive symptoms and well-being may be largely explained by lifestyle factors and adiposity, highlighting the potential importance of promoting a healthy lifestyle in the treatment of depressive disorders.

High-fat diets promote peritoneal inflammation and augment endometriosis-associated abdominal hyperalgesia.

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure to HFD. Increased expression of pain-related mediators in the dorsal root ganglia was observed after lesion induction under the HFD condition. Although HFD did not affect inflammatory macrophages in the peritoneal cavity without lesion induction, the diversity and composition of the gut microbiota were clearly altered by HFD as a sign of low-grade systemic inflammation. Thus, HFD alone might not establish a local inflammatory environment in the pelvic cavity, but it can contribute to further enhancing chronic inflammation, leading to the exacerbation of endometriosis-associated abdominal hyperalgesia following the establishment and progression of the disease.

Elevated circulating procathepsin L as a potential biomarker of inflamm-aging

Inflamm-aging is a condition of low-grade and chronic systemic inflammation characterized by a systemic increase in multiple inflammatory biomarkers such as tumor necrosis factor (TNF), interleukin 6 (IL-6), C-reactive protein (CRP), and CXCL9 (MIG) in experimental and clinical settings. However, despite the recent identification of extracellular procathepsin L (pCTS-L) as a novel mediator of inflammatory diseases such as sepsis, its possible role in inflamm-aging was previously not investigated. In the present study, we compared blood levels of pCTS-L and other 62 cytokines and chemokines between young and aged Balb/C mice by Western blotting and Cytokine Antibody Arrays. In light of the surprising finding of a marked increase in blood pCTS-L levels in aged mice, we propose that blood pCTS-L levels may serve as another biomarker of inflamm-aging. Given the capacity of pCTS-L in inducing various cytokines (e.g., TNF and IL-6), it will be important to test the hypothetic role of pCTS-L in inflamm-aging under experimental and clinical conditions.