Low-grade Inflammatory Activity Research Articles

Peer support as moderator of association between socioeconomic status and low-grade inflammation in adolescents.

Individuals who grow up in low-socioeconomic status (SES) families are at an increased risk of health problems across the lifespan. Although supportive social relationships are postulated to be a protective factor for the health of these individuals, the role of friend support in adolescence is not well understood. Given that low-grade inflammation is one key biological mechanism proposed to explain links between family SES and health outcomes, we examined whether adolescents' friend support buffers the association between family SES and low-grade inflammation among adolescents. 277 dyads of adolescents (63.5% female; 39.4% White, 38.3% Black, and 32.1% Hispanic; Mage = 13.92 years) and one of their parents participated in this longitudinal study (two waves approximately 2 years apart). Parents reported family objective SES (i.e., income, savings, and education) and family subjective SES (i.e., subjective social status). Adolescents reported perceived friend support. Fasting antecubital blood was drawn from adolescents at both visits. Low-grade inflammatory activity was represented by a composite of inflammatory biomarkers and numbers of classical monocytes. Adolescents' friend support moderated the associations of family subjective SES with both the inflammation composite and classical monocyte counts across cross-sectional, longitudinal, and prospective change (only significant for the inflammation composite) analyses. Specifically, lower family subjective SES was associated with higher levels of low-grade inflammation only among adolescents lower, but not higher, in friend support. No moderation was observed for objective SES. Supportive peer relationships buffer the link between family subjective, but not objective, SES and low-grade inflammation in adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Oral phospholipidic curcumin in juvenile idiopathic arthritis-associated uveitis.

To evaluate the efficacy and the safety of curcumin-phosphatidylcholine complex in children affected by juvenile idiopathic arthritis-associated uveitis as an adjunctive treatment to chronic systemic immunosuppressive therapy. In this retrospective, longitudinal study, we treated patients affected by juvenile idiopathic arthritis-associated uveitis with residual low-grade inflammatory activity in the anterior chamber with one tablet of curcumin-phosphatidylcholine complex per day, over a year. Low-grade inflammatory activity was characterized by flare 1+ at slit-lamp examination and 10-50 photon counts per ms) at the FC500 laser flare meter. Inactivity of uveitis was defined as complete disappearance of flare at the slit-lamp examination and values <10 ph/ms at laser flare meter. Conversely, recurrence of the uveitis was defined as a one-step increase from baseline in anterior chamber cells levels or laser flare meter measurements >50 ph/ms. A total of 22 out of 27 patients (81%) achieved inactivity at the end of the study. Five patients (19%) did not show a significant reduction in anterior chamber flare, remaining stable throughout the follow-up. Only three episodes of flare-ups in three different patients were recorded. Overall, the treatment was well tolerated by all patients and no ocular discomfort, ocular side effects, or allergic reactions were registered. Adjunctive therapy with curcumin in patients affected by juvenile idiopathic arthritis-associated uveitis improves mild chronic anterior chamber flare and presents a good safety profile. Despite being mild, anterior chamber inflammation should be minimized to avoid the development of sight-threatening complications in these patients.

Age-dependent alterations in serum cytokines, peripheral blood mononuclear cell cytokine production, natural killer cell activity, and prostaglandin F2α.

This study aimed to determine age-dependent alterations in serum cytokines, peripheral blood mononuclear cell (PBMC) cytokine production, natural killer (NK) cell activity, and urinary 8-epi-prostaglandin F2α (PGF2α). Nine hundred eighty-seven healthy and nonobese subjects were divided into five age groups: 20-34 (group 1), 35-44 (group 2), 45-54 (group 3), 55-64 (group 4), and 65-80 (group 5) years of age. After adjusting for BMI, sex, and smoking and drinking status, serum interferon (IFN)-γ levels decreased in groups 3, 4, and 5 compared with those in groups 1 and 2. Production of IFN-γ by unstimulated PBMCs was lower in the older groups (groups 4 and 5) than in the younger groups (groups 1 and 3). Serum interleukin (IL)-12 was lower in group 5 than in groups 1 and 2. In contrast, both serum and PBMC IL-6 were higher in group 5 than in groups 1, 2, and 3. Urinary 8-epi-PGF2α increased in group 3 compared with that in group 1 and further increased in group 5. Multiple linear regression analysis revealed that serum IFN-γ levels were negatively affected by age, and NK cell activity at a ratio of E:T=5:1 was positively affected by PBMC IFN-γ. This study shows the age-related reductions in serum and PBMC IFN-γ and serum IL-12 and age-related increases in serum and PBMC IL-6 and oxidative stress in healthy nonobese subjects. Additionally, circulating IL-6 levels may be a better marker of the chronic low-grade inflammatory activity associated with aging than systemic levels of high-sensitivity C-reactive protein, TNF-α, and IL-1β.

TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation.

Obesity is accompanied by the activation of low-grade inflammatory activity in metabolically relevant tissues. Studies have shown that obesity-associated insulin resistance results from the inflammatory targeting and inhibition of key proteins of the insulin-signaling pathway. At least three apparently distinct mechanisms-endoplasmic reticulum stress, toll-like receptor (TLR) 4 activation, and changes in gut microbiota-have been identified as triggers of obesity-associated metabolic inflammation; thus, they are expected to represent potential targets for the treatment of obesity and its comorbidities. Here, we review the data that place TLR4 in the center of the events that connect the consumption of dietary fats with metabolic inflammation and insulin resistance. Changes in the gut microbiota can lead to reduced integrity of the intestinal barrier, leading to increased leakage of lipopolysaccharides and fatty acids, which can act upon TLR4 to activate systemic inflammation. Fatty acids can also trigger endoplasmic reticulum stress, which can be further stimulated by cross talk with active TLR4. Thus, the current data support a connection among the three main triggers of metabolic inflammation, and TLR4 emerges as a link among all of these mechanisms.

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Characterization of IBS‐like symptoms in patients with ulcerative colitis in clinical remission

Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Ninety-four patients with new onset of UC were followed prospectively during 3years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score ≤2 and an endoscopic subscore ≤1, with no relapse during the 3-month period prior to visit. The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological well-being and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity.

Metabolic Syndrome and Inflammation: A Critical Review ofIn Vitroand Clinical Approaches for Benefit Assessment of Plant Food Supplements

Metabolic syndrome is defined as the clustering in an individual of several metabolic abnormalities associated with insulin resistance, type 2 diabetes, and obesity, in which low-grade chronic inflammatory activity is commonly observed. Part of the European Project PlantLIBRA is concerned with methods to assess the benefits of plant food supplements (PFSs) in countering inflammatory activity and metabolic syndrome. This paper summarizes the current methods used for benefit assessment of PFS, taking into consideration only in vitro, in silico, and clinical methodologies used to investigate the anti-inflammatory properties of plants. No in silico studies (using computer simulation) related to metabolic syndrome were found; these methods appear to be used exclusively for identifying or testing potentially effective compounds in drug development. Most in vitro methods for the assessment of beneficial effects of botanicals or plant food supplements in diabetes were based on a quantitative polymerase chain reaction (PCR), whereas the preferred kind of clinical study was the double-blind randomized controlled clinical trial. Only two parameters were observed to change after treatment with botanicals in both in vitro and in vivo studies: interleukin-6 and tumour necrosis factor-α, and these biomarkers should be carefully considered in future studies for PFS benefit assessment.

Interaction between cytokine gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in older women: study protocol for a randomized controlled trial

BackgroundAging is associated with chronic low-grade inflammatory activity with an elevation of cytokine levels. An association between regular physical activity and reduction of blood levels of anti-inflammatory cytokines is demonstrated in the literature pointing to an anti-inflammatory effect related to exercise. However, there is no consensus regarding which type of exercise and which parameters are the most appropriate to influence inflammatory markers. Evidence indicates that the single nucleotide polymorphism (SNP) can influence the synthesis of those cytokines affecting their production.Methods/DesignThe design of this study is a randomized controlled trial. The aim of this study is to investigate the interaction between the cytokine genes SNP and the effect of physical activity on older women. The main outcomes are: serum levels of sTNFR-1, sTNFR-2, interleukin (IL)-6, IL-10, measured by the ELISA method; genotyping of tumor necrosis factor- (TNF)-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896) by the TaqMan Method (Applied Biosystems, Foster City, CA, USA); and physical performance assessed by Timed Up and Go and 10-Meter Walk Tests. Secondary outcomes include: Geriatric Depression Scale, Perceived Stress Scaleand aerobic capacity, assessed by the six-minute walk; and lower limb muscle strength, using an isokinetic dinamometer (Biodex Medical Systems, Inc., Shirley, NY,USA). Both exercise protocols will be performed three times a week for 10 weeks, 30 sessions in total.DiscussionInvestigating the interaction between genetic factors and exercise effects of both protocols of exercise on the levels of inflammatory cytokine levels can contribute to guide clinical practice related to treatment and prevention of functional changes due to chronic inflammatory activity in older adults. This approach could develop new perspectives on preventive and treatment proposals in physical therapy and in the management of the older patient.Trial registration(ReBEC) RBR9v9cwf

From Risk Factors to Structural Heart Disease: The Role of Inflammation

Elevated levels of circulating proinflammatory cytokines and adipokines have been repeatedly associated with increased risk for clinically manifest (Stage C) heart failure in large cohort studies. However, the role of low-grade, subclinical inflammatory activity in the transition from risk factors (Stage A heart failure) to structural heart disease (Stage B heart failure) is less well understood. Recent evidence suggests that chronic low-grade inflammatory activity is involved in most mechanisms underlying progression of structural heart disease, including ventricular remodeling after ischemic injury, response to pressure and volume overload, and myocardial fibrosis. Inflammation also contributes to progression of peripheral vascular changes.

Depression Symptoms, Low-Grade Inflammatory Activity, and New Targets for Clinical Intervention

Depression Symptoms, Low-Grade Inflammatory Activity, and New Targets for Clinical Intervention

Reduced Th2 cytokine production by sarcoidosis patients in clinical remission with chronic fatigue

When the inflammatory phase of sarcoidosis has resolved, complaints of chronic fatigue frequently persist. Low-grade residual inflammatory activity may play a role in maintaining chronic fatigue. The aim of this study was to compare in vitro cytokine/chemokine production and plasma cytokine/chemokine levels between chronically fatigued and non-fatigued patients with sarcoidosis in clinical remission. Patients with sarcoidosis in clinical remission were assigned to a non-fatigued group (n=38) or a fatigued group (n=34) based on the standardized cut-off of the fatigue questionnaire Checklist Individual Strength. Cytokines/chemokines in plasma and in supernatants of whole blood cultures stimulated with either a T cell mitogen or lipopolysaccharide were quantified by multiplex analysis. Associations of cytokine/chemokine profiles with chronic fatigue were analyzed by multivariate analysis of variance and principal component analysis followed by logistic regression. Principal component analysis of T cell mitogen-induced cytokine/chemokine production identified three components that explained 76% of the variance in the cytokine/chemokine data. Logistic regression revealed that the 'Th2 cytokine'-component which mainly consists of interleukin (IL)-4, IL-5 and IL-10 was significantly and negatively associated with chronic fatigue. In addition, multivariate analysis revealed higher levels of LPS-induced IL-8 and lower levels of plasma monocyte chemoattractant protein (MCP)-1 in the fatigued group compared to the non-fatigued group. In chronically fatigued sarcoidosis patients in clinical remission, we found a cytokine/chemokine profile which is suggestive for a less competent Th2 counterbalancing capacity, that may contribute to the persistence of chronic fatigue.

High-Mobility Group Box-1 Protein (HMGB1) Is Increased in Antineutrophilic Cytoplasmatic Antibody (ANCA)-Associated Vasculitis with Renal Manifestations

High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is increasingly recognized as an important proinflammatory mediator actively secreted from monocytes and macrophages and passively released from necrotic cells. In antineutrophilic cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), the kidneys are commonly affected vital organs, characterized by focal necrotizing and/or crescentic pauci-immune glomerulonephritis. The aim of the study was to determine whether HMGB1 serum levels are elevated in AAV with renal manifestations. A total of 30 AAV patients (16 female and 14 male; median age 59 years, range 17-82) with Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome with available renal biopsies and serum samples were included. In seven cases, serum was also obtained at rebiopsy in remission. HMGB1 was analyzed with Western blot. Birmingham Vasculitis Activity Score (BVAS, version 2003), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinanalysis, creatinine, estimated glomerular filtration rate, sex and age were included in the analysis. Twenty-five episodes of biopsy-proven active disease with BVAS 17.9 ± 4.6 and 13 cases with inactive biopsies and BVAS 2.3 ± 3.7 (P = 0.0001) were identified. CRP, ESR, hematuria and proteinuria were significantly higher in active cases. HMGB1 was significantly elevated (P = 0.01) comparing active with inactive cases (120 ± 48 versus 78 ± 46 ng/mL) and significantly lower in the seven control patients (P = 0.03) at rebiopsy in remission. HMGB1 remained higher in inactive cases compared with historic healthy controls (10.9 ± 10.5 ng/mL). HMGB1 levels did not differ significantly between AAV subgroups. CRP and ESR did not correlate with HMGB1. HMGB1 is significantly increased in AAV with renal involvement. Residual HMGB1 elevation in remission could possibly reflect low-grade inflammatory activity or tissue damage. Future studies may further reveal whether HMGB1 is useful as a marker of disease activity and a predictor of outcome in AAV.

Biological clock changes in the aging brain

Biological clock changes in the aging brain

Zinc Supplementation in the Elderly Reduces Spontaneous Inflammatory Cytokine Release and Restores T Cell Functions

Aging is associated with low-grade inflammation on the one hand and mild zinc deficiency on the other. These conditions contribute to decreased immune functions, resulting in increased incidences of infections and autoimmune diseases. The aim of this study was to give more insight into the question, to what extent is low-grade inflammation caused by zinc deficient status. Here we report the effect of improved intracellular zinc status on low-grade inflammatory activity in 19 healthy elderly subjects. Our experiments show that adjustment of labile zinc by moderate zinc supplementation reduces spontaneous cytokine release and defects in termination of inflammatory activity. This results in reduced amounts of unspecific preactivated T cells and leads to improved T cell response upon mitogenic stimulation. Therefore, in contrast to other anti-inflammatory drugs, zinc does not suppress, but improves immune reaction upon pathogen invasion. These results suggest that mildly zinc-deficient, healthy elderly subjects might benefit from moderate zinc supplementation due to a more balanced immune response with reduced incidences of infections and autoimmune diseases.

Relationship between heart rate variability, interleukin-6, and soluble tissue factor in healthy subjects

Decreased heart rate variability (HRV) has been associated with an increased risk of atherosclerosis. We hypothesized that a decrease in frequency domains of resting HRV would be associated with elevated plasma levels of interleukin (IL)-6 and soluble tissue factor (sTF) both previously shown to prospectively predict atherothrombotic events in healthy subjects. Subjects were 102 healthy and unmedicated black and white middle-aged men and women. We determined IL-6 and sTF antigen in plasma and HRV measures from surface electrocardiogram data using spectral analysis. All statistical analyses controlled for age, gender, ethnicity, smoking status, blood pressure, and body mass index. Low amounts of low frequency (LF) power (β=−0.31, p=0.007) and high frequency (HF) power (β=−0.36, p=0.002) were associated with increased amounts of IL-6, explaining 7% and 9% of the variance, respectively. Interactions between LF power and IL-6 (p=0.002) and between HF power and IL-6 (p=0.012) explained 8% and 5%, respectively, of the variance in sTF. Post hoc analyses showed associations between IL-6 and sTF when LF power (β=0.51, p<0.001) and HF power (β=0.48, p<0.001) were low but not when LF power and high HF power were high. The findings suggest that systemic low-grade inflammatory activity is associated with a decrease in HRV. Furthermore, there was a positive relationship between plasma levels of IL-6 and sTF antigen when HRV was low. Inflammation and related hypercoagulability might particularly contribute to atherothrombotic events in a setting of decreased HRV.

C-reactive protein: a marker or a player?

It has been suggested that Type 2 diabetes may, in part, be precipitated or accelerated by an acute-phase reaction as part of the innate immune response, in which large amounts of cytokines are released from adipose tissue, creating a low-grade inflammatory milieu. There is also firm evidence that atherosclerosis is an immune-mediated inflammatory disease. Therefore it is reasonable to imply that low-grade inflammation is an important pathogenetic factor in atherosclerosis and cardiovascular events in patients with Type 2 diabetes. Over the last few years, there have been a lot of promising clinical markers proposed to link inflammation and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive protein) might be a prognostic marker for further cardiovascular events, although this has been refuted recently. In this issue of Clinical Science, Castoldi and co-workers have demonstrated that, in patients with Type 2 diabetes categorized into low (<1.0 mg/l), medium (1.0-3.0 mg/l) and high (>3.0 mg/l) hs-CRP groups, serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of interleukin-1beta and interleukin-6 in whole blood. This finding may indicate that low-grade inflammatory activity might influence cytokine production in these patients.

Mast cell tryptase: a new biomarker in patients with stable coronary artery disease

Mast cells may participate actively in the inflammatory process of atherosclerotic plaques by releasing proteolytic enzymes and various other pro-inflammsatory substances. We hypothesized that increased levels of mast cell tryptase, could be an important biomarker in patients with stable coronary artery disease (CAD). We measured tryptase in 102 patients without acute coronary syndromes undergoing cardiac catheterization. Patients with significant CAD [≥50% stenosis in ≥1 artery ( n = 66)] had significantly higher serum tryptase than patients with normal angiography ( n = 13) or non-significant CAD [<50% stenosis ( n = 23)]. The median, 25th and 75th percentiles for tryptase in these two groups were 8.38 (6.4 and 10.7) μg/L versus 6.78 (5.61 and 9.72) μg/L, p = 0.014. Patients in the highest quartile of tryptase levels had a 4.3-fold risk for CAD [Odds ratio (OR): 4.3; 95% confidence interval (CI): 1.08–17.19; p = 0.04]. In a multivariate regression analysis, tryptase remained an independent predictor for CAD along with age (OR: 1.178; 95% CI: 1.021–1.359, p = 0.025). High circulating tryptase levels may be a result of chronic low-grade inflammatory activity present in atherosclerotic plaques. Tryptase measurements may emerge as a novel way of identifying asymptomatic patients with CAD, and represent a new biomarker of therapeutic efficacy in patients with CAD.

Elevated secretory non-pancreatic type II phospholipase A2 serum activity is associated with impaired endothelial vasodilator function in patients with coronary artery disease.

Low-grade inflammatory activity is associated with an increased risk for ischaemic coronary events. sPLA(2) (secretory non-pancreatic type II phospholipase A(2)) serum activity is increased in chronic inflammatory diseases and may also contribute to atherogenesis. Since the endothelium is a major target for inflammatory cytokines, we hypothesized that elevated serum activity of sPLA(2) is associated with an impaired vasodilator function in patients with documented CAD (coronary artery disease). Endothelium-dependent (acetylcholine, 10-50 microg/min) and endothelium-independent (sodium nitroprusside, 2-8 microg/min) FBF (forearm blood flow) responses were measured by venous occlusion plethysmography in 50 male patients with angiographically documented CAD. sPLA(2) serum activity was inversely correlated with acetylcholine-induced FBF responses ( r =-0.36; P <0.05). In addition, there was a significant correlation between sPLA(2) and CRP (C-reactive protein; r =0.33, P <0.02). In contrast, FBF responses to sodium nitroprusside did not correlate with sPLA(2) serum activity. In order to identify independent predictors of an impaired endothelium-dependent vasodilator function in patients with CAD, a multivariate analysis was performed including the inflammatory serum markers as well as classical risk factors of CAD. This analysis demonstrated that both sPLA(2) ( P <0.05) and CRP serum levels ( P <0.05) were the only significant independent predictors of an impaired acetylcholine-induced FBF response. In conclusion, elevated sPLA(2) serum activity is associated with a significant impairment in systemic endothelial vasodilator function in patients with CAD. The identification of sPLA(2) as a novel independent predictor for endothelial dysfunction provides another important clue to link a systemic marker of inflammation with coronary atherosclerotic disease.

Age-related inflammatory cytokines and disease.

Aging is associated with chronic low-grade increases in circulating levels of inflammatory markers. A wide range of environmental factors, including smoking, infections, and obesity, genetic factors, and the declining function of sex hormones may contribute to systemic low-grade inflammatory activity in older individuals. Age-associated disease may exacerbate this phenomenon. The multifunctional cytokines TNF-alpha and IL-6 have been associated with morbidity and mortality in the elderly. Evidence supports the direct role of TNF-alpha in the pathogeneses of atherosclerosis, type 2 DM, and AD in older individuals. Age-related increases in systemic levels of TNF-alpha could provide a unifying basis for these disorders. Furthermore, TNF-alpha induces a catabolic state that causes frailty. Circulating levels of IL-6 seem to be a strong risk factor for frailty in the elderly, which could reflect its association with increased production of TNF-alpha. IL-6 also may be a risk factor for thromboembolic complications. In healthy, elderly populations, high circulating levels of TNF-alpha and IL-6 predict mortality, independent of comorbidity, indicating that TNF-alpha and IL-6 cause morbidity and mortality. In cohorts of frail, older individuals, TNF-alpha and IL-6 also act as disease markers. Circulating levels of TNF-alpha seem to be the best predictor of mortality in frail, elderly populations with a high mortality rate, whereas IL-6 seems to be the strongest risk marker in healthy, elderly populations. This finding could reflect that in relatively healthy old populations the increase in circulating levels of IL-6 represent a systemic response to local proinflammatory activities; however, when age-related inflammatory diseases progress, levels of TNF-alpha increase in the circulation and become gradually a stronger risk marker than IL-6. In conclusion low-grade elevations in levels of circulating cytokines are strong independent risk factors of morbidity and mortality in the elderly, and lifestyle factors and comorbidities may modulate these levels. Exercise and dietary interventions may be possible strategies to decrease inflammatory activity and improve the health status of the elderly.

Asymptomatic bacteriuria in elderly humans is associated with increased levels of circulating TNF receptors and elevated numbers of neutrophils

Low-grade inflammatory activity is strongly associated with age-associated diseases such as atherosclerosis, dementia, type-2 diabetes, sarcopenia, and osteoporosis and predicts mortality risk in elderly populations. The aim of the current study was to investigate if asymptomatic bacteriuria in elderly humans was associated with inflammation. Midstream clean-catch urine culture was collected from consecutive, elderly patients at admission to a department of internal medicine due to functional disability. Forty patients (age 70–91 years) were selected and included in the current study; 20 subjects had positive urine culture and 20 sex- and age-matched subjects had negative urine culture. Inclusion criteria were temperature below 37.8 °C, no clinical signs of infection and no current antibiotic treatment. Patients with asymptomatic bacteriuria had significantly increased levels of circulating tumor necrosis factor receptors (sTNFR-I) and a higher number of neutrophils in the blood compared to the group without bacteriuria. Thus, the present study provides some support for the hypothesis that asymptomatic urinary infections are associated with low-grade immune activity in frail, elderly humans.