Lower Concentrations Of IL-10 Research Articles

7938 Validation of Inflammatory Cytokine Multiplex Array With Variations in Target Panel

Abstract Disclosure: W.M. Sanders: None. C.A. Karvonen-Gutierrez: None. D.S. McConnell: None. Background: Multiplex arrays are an invaluable tool for conducting large-scale biomarker research as they provide a high-throughput, cost-effective method for quantifying a panel of endocrine markers. However, the shared reaction environment between antibodies of differing reactivities creates the potential for inducing a technical difference in the assay methods due to any variation in panel selection. Methods: We evaluated the R&D Systems Luminex HS Cytokine Panel A (Catalog # FCSTM09) for systematic differences when measuring a “panel” of IL-1β, TNF-α, and IL-10 vs. measuring “IL-10 only.” We selected 72 serum samples and assayed them in singleton 4 times: 2 separate “panel” batches, and 2 separate “IL-10 only” batches. Differences in log-transformed IL-10 results for sample replicates within and between the “panel” and “IL-10 only” batches were assessed for significance with paired t-tests (α=.01). We also assessed the differences graphically with Bland-Altman plots of differences and absolute percent differences.All batches included control materials from R&D Systems and internal lab serum pools (male and female). To retroactively assess the test batches, we graphically compared their quality control results to those of the subsequent, larger assay project we were piloting. Results: The “IL-10 only” assay yielded an average result of .879 pg/mL (SD .57) on batch 1 and .712 pg/mL (SD .58) on batch 2, with an average paired sample difference of .167 pg/mL, and an average absolute percent difference of 28.8%. The “panel” assay produced an average IL-10 result of .645 pg/mL (SD .50) on batch 1 and .720 pg/mL (SD .52) on batch 2, with an average paired sample difference of .075 pg/mL, and an average absolute percent difference of 15.5%. Comparing pooled IL-10 results from the “IL-10 only” batches with the “panel” batches, there was an average paired difference of .113 pg/mL and absolute percent difference of 16.2%. Paired t-testing of log-transformed results for within “panel,” within “IL-10 only,” and between pooled results from the two methods demonstrated that each had significant differences (p<.0001). The Bland-Altman plots further revealed that these differences were ubiquitously large for samples with low concentrations of IL-10.Test batch quality control results were consistent with those in the primary assay project. The serum pool QCs exhibited significant inter-assay variation – the male pool average result was .41 pg/mL (SD .10) vs. .359 in the test batches, and the female pool average was .57 pg/mL (SD .10) vs. .548 in the test batches. Conclusion: The multiplex assay had considerable inter-assay variation at low concentrations of IL-10, and low results were prevalent. Due to this, we determined that any methodological differences between the “panel” and “IL-10 only” methods were undetectable compared to ambient variation, and irrelevant given the sample characteristics. Presentation: 6/3/2024

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study

BackgroundType 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population.MethodsThis was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1β and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes.ResultsPrediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1β and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1β and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05).ConclusionsSFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Determinants of persistent symptoms after treatment for Lyme borreliosis: a prospective observational cohort study

Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology. In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n=4000 and n=2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice). Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in exvivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms. Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated. Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS).

Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy

CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study

BackgroundStaphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus.MethodsAn in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 μL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 μL of 10–2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO−2); and hydrogen peroxide (H2O2) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO−2, and H2O2. The HPBMs were then removed for the analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05.ResultsOur data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO−2, and H2O2 when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO−2, and H2O2. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs.ConclusionsWe found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

Clinical and Immunological Markers of Pulmonary Impairment Among People With HIV in India.

BackgroundDespite antiretroviral therapy, chronic lung diseases remain an important source of morbidity and mortality in people with HIV (PWH). We sought to identify clinical and immunological markers of pulmonary impairment among PWH in India.MethodsTwo hundred ten adult PWH receiving antiretroviral therapy (ART) were prospectively evaluated for 3 years. Plasma concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor alpha, D-dimer, C-reactive protein, soluble (s)CD14, and sCD163 were measured at enrollment. We used multivariable linear and logistic regression to measure the association of baseline and time-varying clinical and immunological variables with spirometry-defined chronic obstructive pulmonary disease (COPD), restrictive spirometry pattern (RSP), preserved ratio impaired spirometry (PRISm), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) during the third year of follow-up.ResultsAfter adjusting confounders, females were 7 times more likely to have RSP (95% CI, 2.81 to 17.62; P < .001) and 22 times more likely to have PRISm (95% CI, 7.42 to 69.92; P < .001) compared with men. Higher IL-6 concentrations were associated with lower FEV1 z-scores (β, −0.14 per log-higher; 95% CI, −0.29 to 0.008; P = .06) and higher odds of COPD (adjusted odds ratio [aOR], 2.66 per log-higher; 95% CI, 1.16 to 6.09; P = .02). Higher D-dimer concentrations were associated with lower FVC z-scores (β, −0.40 per log-higher; 95% CI, −0.78 to −0.01; P = .04). Conversely, higher IL-10 concentrations were associated with lower odds of PRISm (aOR, 0.76 per log-higher; 95% CI, 0.59 to 0.99; P = .04).ConclusionsFemale sex, higher concentrations of IL-6 and D-dimer, and lower concentrations of IL-10 were associated with pulmonary impairment in adult PWH receiving ART in India.

Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes.

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.

Influence of rs6667202 SNP on Interleukin-10 levels in the gingival fluid of patients with periodontitis grade C

Grade C periodontitis in youngers is characterized by a severe form of periodontitis, and IL10 rs6667202 single nucleotide polymorphism (SNP) has been described as an important feature in this disease etiology. Aim: This study aimed to evaluate, in vivo, the functionality of IL10 rs6667202 SNP on IL-10 gingival fluid levels. Methods: Thirty patients with Perio4C were selected, 15 with the IL10 AA genotype (rs6667202) and 15 with AC/CC genotypes. The gingival fluid was collected from two sites with probing depth ≥ 7 mm and bleeding on probing, and two healthy sites. The IL-10 concentration was determined by Luminex/MAGpix platform. Results: In deep pockets, the IL10 AA genotype presented a lower concentration of IL-10 when compared with AC or CC genotypes (p&lt;0.05). In shallow pockets, no difference between groups was seen (p&gt;0.05). Conclusion: IL10 rs6667202 SNP decreases the production of IL-10 in crevicular fluid, potentially affecting this disease progression.

Modern views on the role of the immune system in the development of preeclampsia (overview)

Hypertensive disorders during pregnancy are associated with high maternal and perinatal mortality, so it is very important for obstetricians to recognize severe cases with poor prognosis in time.One of the pathogenesis of preeclampsia is an increase in TNF-alpha and IL-6 levels. In this regard, the researchers wanted to know the expression level of TNF-alpha and interleukin-6 in pregnant women with preeclampsia. In preeclampsia, in contrast to normal pregnancy, the cytokine profile changes - there are higher concentrations of IFN-y, TNF-a, IL-6, IL-1fi, IL-8 and IL-16, and lower concentrations of IL-10.Although the final pathogenesis of this pathology remains to be determined, on the basis of this it will be possible to develop an adequate therapy algorithm to save the life of the mother and child.

Кореляційні зв’язки між цитокіновими показниками імунного запалення, ендотеліальним фактором росту та біохімічними параметрами у пацієнтів з подагрою

The correlations between cytokine status, vascular endothelial growth factor (VEGF) content, clinical and biochemical parameters in patients with various forms of gout were studied to improve the algorithm for monitoring of clinical condition and effectiveness of treatment. For patients with gout and volunteers clinical and biochemical studies were performed. The content of interleukins (IL-1β, IL-17, IL-22, IL-10), tumor necrosis factor alpha (TNF-α) and VEGF were investigated. Concentrations of TNF-α, IL-1β and IL-17 characterized of inflammation intensity at all stages of gout and increased linearly as the disease progressed. At the stage of asymptomatic hyperuricemia, there were an increased (75% of the control group) concentration of IL-22 on the background of lymphopenia, low concentrations of IL-10 and VEGF. This indicates that the content of IL-22 is a potentially informative biomarker of inflammation intensity as well as a possible predictor of the development of immune-dependent complications and vascular catastrophes in the early stages of gout without signs of joint damage. The concentration of TNF-α positively correlates with the content of IL-10 (r = 0.534); whereas the concentration of IL-1β is independent of the content of IL-10. The relationship between IL-1β and VEGF concentrations (r = 0.40) suggests that IL-1β is more closely associated with endothelial dysfunction and the risk of vascular complications. IL-22 levels do not correlate with other cytokine status, but are associated with lymphocyte counts, so signs of Th22-dependent immune inflammation may be a potential biomarker of lymphocytic depression status in gout. Cytokine status changes in different phases and stages of hyperuricemia. Comparing these changes with the clinical and laboratory picture improves monitoring of the disease development and effectiveness of treatment.

Subgingival endotoxin and lipoteichoic acid modulate cytokine production in diabetic subjects: A Case-control Study.

Periodontal disease and diabetes mellitus (DM) are highly prevalent and interrelated diseases, resulting in altered host response microbiota. Thus, this study aimed to evaluate the impact of DM on local levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and their relationship with cytokines and matrix metalloproteinases' (MMPs) profile. This case-control study included diabetic (n=15) and non-diabetic (n=15) subjects presenting Stage 3-4, Grade C, Periodontitis. Gingival crevicular fluid (GCF) was collected, and LPS and LTA levels were analyzed by enzyme-linked immunosorbent assay (ELISA), while IFN-γ, IL-10, IL-17, IL-1β, IL-4, MMP-2, and MMP-9 were measured by LUMINEX/MAGpix. Mann-Whitney and Spearman's correlation tests were used to compared and to correlate variables (p<0.05). Higher levels of LTA, LPS, IL-10, IL-1β, and MMP-2 (p<0.05) and lower levels of IL-17 were found in the DM group (p<0.05). Non-diabetic subjects presented higher LPS, IFN-γ, IL-17, and MMP-2 levels and lower IL-10 concentration (p<0.05). No significant correlation was seen between LPS and cytokine profile in non-diabetic. Local levels of LTA were positively correlated with IL-17 and MMP-2 and negatively with IL-10. LTA and LPS drove the inflammatory profile through the modulation of cytokines and MMPs in a different manner in DM and non-diabetic subjects.

Gum arabic reduces inflammation, oxidative, and nitrosative stress in the gastrointestinal tract of mice with chronic kidney disease.

The aim of this study was to investigate some biochemical indices of inflammation and oxidative and nitrosative stresses in the gastrointestinal tract of mice with experimental chronic kidney disease (CKD) and treated with gum arabic (GA). Male CD1 mice (n = 28) were randomly distributed into four groups and treated for four consecutive weeks: group 1: Control: received the same diet without treatment until the end of the study; group 2: Adenine: switched to a powder diet containing adenine (0.2% w/w in feed); group 3: Gum acacia (GA): given normal feed and GA in drinking water at a concentration of 15% w/v; and group 4: Adenine + GA: given adenine in the feed as in the second group plus GA in the drinking water at concentration of 15% w/v. CKD was induced to mice by adenine feeding and concomitantly treated with the prebiotic dietary fiber gum acacia, GA (15% in drinking water). Duodenal mucosa from CKD mice had significantly higher concentrations of TNF-alfa, IL- 6, and TGF-beta-1 and lipid peroxidation. Moreover, low concentrations of IL-10, some antioxidants (catalase, glutathione reductase, total antioxidant capacity, and superoxide dismutase), and nuclear factor erythroid 2-related factor 2 were found in the duodenum. The levels of nitrosative stress (nitrite, nitrate, and total nitrate) were significantly increased by CKD, as well as the concentrations of ammonia and urea creatinine in the cecal content. Concomitant GA treatment significantly mitigated these harmful effects. Taken together, GA reduces inflammation and duodenal oxidative and nitrosative stress in the gastrointestinal tract of mice with CKD.

Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: a case-control study.

Decrease in soluble anti-aging Klotho protein levels is associated to cardiovascular disease (CVD). Diverse studies have shown a bidirectional relationship between Klotho and inflammation, a risk factor for the development of CVD. In this work we aimed to evaluate the association between Klotho and inflammatory cytokines levels in the context of human CVD.The study included 110 patients with established CVD and preserved renal function, and a control group of 22 individuals without previous history of cardiovascular events. Serum Klotho and IL10 levels were significantly lower in the CVD group. Inflammatory status, marked by the TNFα/IL10 ratio and the C-reactive protein (CRP) levels, was significantly increased in the group of patients with established CVD. Soluble Klotho levels were directly correlated with eGFR (r=0.217) and IL10 (r=0.209) and inversely correlated with age (r=-0.261), CRP (r=-0.203), and TNFα/IL10 (r=-0.219). This association with TNFα/IL10 remained significant in age-matched subgroups. Multiple logistic regression analysis showed that age, smoking and the neutrophil-to-lymphocyte ratio (NLR) constituted risk factors for the presence of CVD, while Klotho was a protective factor.In conclusion, in patients with established CVD, the reduction in soluble Klotho is associated with a pro-inflammatory status marked by lower IL10 concentrations and higher TNFα/IL10 ratio and CRP levels.

CD163 deficiency facilitates lipopolysaccharide‐induced inflammatory responses and endotoxin shock in mice

ObjectivesSeptic (or endotoxin) shock is a severe systemic inflammatory disease caused by bacteraemia or endotoxaemia. Although it is known that increased serum levels of CD163 are observed in septic/endotoxin shock patients, the exact function and significance of CD163 in macrophage activation remain unclear. Therefore, in the current study, we tested whether CD163 contributes to the pathogenesis of endotoxin shock in mice.Methods and resultsIn samples obtained from autopsy, the number of CD163‐positive macrophages was increased in the kidney, liver, heart, bone marrow and spleen of patients who had died from septic/endotoxin shock when compared to patients who had died from other causes. The animal study revealed a significantly lower survival rate in CD163‐deficient mice after lipopolysaccharide (LPS) injection. Several cytokines and oxidative stress‐related molecules were significantly elevated in the sera of LPS‐induced endotoxin shock mice models. Higher concentrations of IL‐6, TNF‐α, IL‐1β, nitrite (NO2‐) and nitrate (NO3‐) and a lower concentration of IL‐10 were observed in CD163‐deficient mice treated with LPS. Similar results were observed in CD163‐deficient LPS‐stimulated macrophages. Furthermore, in an antitype II collagen antibody‐induced arthritis (CAIA), rheumatoid arthritis model, inflammation and bone erosion scores as well as the expression of IL‐6 and IL‐1β were significantly increased in CD163‐deficient mice.ConclusionsCD163 was suggested to be involved in the regulation of inflammatory cytokine expression in septic/endotoxin shock and CAIA.

Salivary Cytokine Biomarker Concentrations in Relation to Obesity and Periodontitis.

Systemic low-grade inflammation is associated with obesity. Our aim was to examine the association between obesity and salivary biomarkers of periodontitis. Salivary interleukin (IL)-1-receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α concentrations were measured from 287 non-diabetic obese (body mass index (BMI) of >35 kg/m2) individuals and 293 normal-weight (BMI of 18.5–25 kg/m2) controls. Periodontal status was defined according to a diagnostic cumulative risk score (CRS) to calculate the risk of having periodontitis (CRS I, low risk; CRS II, medium risk; CRS III, high risk). In the whole population, and especially in smokers, higher IL-8 and lower IL-10 concentrations were detected in the obese group compared to the control group, while in non-smoking participants, the obese and control groups did not differ. IL-1Ra and IL-8 concentrations were higher in those with medium or high risk (CRS II and CRS III, p < 0.001) of periodontitis, whereas IL-10 and TNF-α concentrations were lower when compared to those with low risk (CRS I). In multivariate models adjusted for periodontal status, obesity did not associate with any salivary cytokine concentration. In conclusion, salivary cytokine biomarkers are not independently associated with obesity and concentrations are dependent on periodontal status.

Metabolic syndrome agravates cardiovascular, oxidative and inflammatory dysfunction during the acute phase of Trypanosoma cruzi infection in mice

We evaluated the influence of metabolic syndrome (MS) on acute Trypanosoma cruzi infection. Obese Swiss mice, 70 days of age, were subjected to intraperitoneal infection with 5 × 102 trypomastigotes of the Y strain. Cardiovascular, oxidative, inflammatory, and metabolic parameters were evaluated in infected and non-infected mice. We observed higher parasitaemia in the infected obese group (IOG) than in the infected control group (ICG) 13 and 15 days post-infection. All IOG animals died by 19 days post-infection (dpi), whereas 87.5% of the ICG survived to 30 days. Increased plasma nitrite levels in adipose tissue and the aorta were observed in the IOG. Higher INF-γ and MCP-1 concentrations and lower IL-10 concentrations were observed in the IOG compared to those in the ICG. Decreased insulin sensitivity was observed in obese animals, which was accentuated after infection. Higher parasitic loads were found in adipose and hepatic tissue, and increases in oxidative stress in cardiac, hepatic, and adipose tissues were characteristics of the IOG group. Thus, MS exacerbates experimental Chagas disease, resulting in greater damage and decreased survival in infected animals, and might be a warning sign that MS can influence other pathologies.

Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma

BackgroundMild equine asthma is a common inflammatory airway disease of the horse. The primary treatment of mild equine asthma is corticosteroids. The purpose of this study was to investigate the effects of injected dexamethasone on relative IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2 and TNF-α mRNA expression in bronchoalveolar lavage (BAL) fluid in healthy Thoroughbred horses (n = 6), and those with mild equine asthma (n = 7).ResultsHorses with mild equine asthma had a significantly greater bronchoalveolar lavage mast cell percentage than healthy horses both before and after treatment. Mild equine asthma was associated with a 4.95-fold up-regulation of IL-17 (p = 0.026) and a 2.54-fold down-regulation of IL-10 (p = 0.049) compared to healthy horses. TNF-α was down-regulated in response to dexamethasone treatment in both healthy horses (3.03-fold, p = 0.023) and those with mild equine asthma (1.75-fold, p = 0.023). IL-5 was also down-regulated in horses with mild asthma (2.17-fold, p = 0.048).ConclusionsHorses with mild equine asthma have a lower concentration of IL-10 in BAL fluid than healthy controls which concurs with human asthmatics. The marked up-regulation of IL-17 in horses with mild asthma suggests these horses had a true tendency of “allergic” airway inflammation in response to environmental allergens. Dexamethasone administration exerted anti-inflammatory effects associated with down-regulation of TNF-α in all horses, and decreased levels of IL-5 mRNA expression in horses with mild equine asthma. The inhibition of the Th-2 response, without any alterations to the airway cytology, indicates that maintained exposure to environmental allergens perpetuates airway inflammation.

ADRB2 GLN27GLU POLYMORPHISM ASSOCIATED WITH ADIPOSITY INDICATORS AND IL-10 IN ADOLESCENTS

ABSTRACT Introduction: Studies of association between obesity and genetic factors have demonstrated a significant contribution of polymorphisms related to body fat distribution and subclinical inflammatory process. Objective: To investigate the association between genotypes of the Gln27Glu polymorphism of the ADRB2 gene and indicators of adiposity, inflammatory markers, metabolic parameters and parameters of physical fitness in overweight adolescents. Methods: A total of 44 male and female adolescents, aged between 13 and 17 years, with positive clinical diagnosis of overweight, were divided into two groups according to the Gln27Glu polymorphism genotypes of the ADRB2 gene: a) Group of carriers of the 27Glu allele (Gln27Glu/Glu27Glu) (n = 22); b) Group of non-carriers of the 27Glu allele (Gln27Gln) (n = 22). Both groups were evaluated for body composition, sexual maturation, cardiorespiratory fitness variables and indicators of muscle strength. Basal glycemia and insulin, lipid profile and inflammatory profile were measured. Abdominal subcutaneous and visceral adiposities were evaluated by ultrasonography. Genotyping of the Gln27Glu polymorphism of the ADRB2 gene was performed by the Taqman allelic discrimination assay. Results: The genotype frequency found was: Gln/Gln (n = 22) (50.0%), Gln/Glu (n = 18) (41.0%) and Glu/Glu (n = 4) %). The frequency of the 27Glu allele was 29.5%. The group of adolescent carriers of the 27Glu allele of the ADRB2 gene presented higher mean adiposity indicators (abdominal circumference, trunk fat mass and visceral fat), as well as lower IL-10 concentrations when compared to non-carriers. Conclusions: The 27Glu allele was associated with adiposity indicators in overweight adolescents, while subcutaneous abdominal fat exhibited an inverse relationship with inflammatory variables and maximum oxygen uptake, which may result in more damage to health. Level of evidence III; Case-control study.

Multi-Stage Fitness Test Performance, V˙O2 Peak and Adiposity: Effect on Risk Factors for Cardio-Metabolic Disease in Adolescents

The role of physical activity in determining the metabolic health of adolescents is poorly understood, particularly concerning the effect on low-grade chronic inflammation (chronic elevation of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and acute phase protein CRP, which is implicated in the etiology of atherosclerosis) and anti-inflammatory mediators such as IL-10. Furthermore, there is limited information on the mediating effects of performance on the multi-stage fitness test (MSFT), O2 peak and adiposity on risk factors for cardio-metabolic disease in adolescents.Purpose: To examine the effect of performance on the MSFT, O2 peak and adiposity on risk factors for cardio-metabolic diseases in adolescents.Methods: Following ethical approval, 121 adolescents (11.3 ± 0.8 year) completed the study. Risk factors for cardio-metabolic disease (circulating inflammatory cytokines, blood glucose and plasma insulin concentrations) was assessed using a fasted capillary blood sample. Participants were separated into quartiles based upon distance ran during the MSFT, the blood lactate response to submaximal exercise, O2 peak (determined during an uphill graded treadmill test), and adiposity (determined as the sum of four skinfolds). The blood lactate response to submaximal exercise and V02 peak were measured in a sub-group of participants. Data were analyzed using two-way between-subjects ANCOVA and multiple linear regression.Results: Participants with the lowest performance on the MSFT had higher blood concentrations of IL-6 (3.25 ± 0.25 pg mL-1) and IL-1β (4.78 ± 0.54 pg mL-1) and lower concentrations of IL-10 (1.80 ± 0.27 pg mL-1) when compared with all other quartiles (all p < 0.05). Yet, when categorized into O2 peak quartiles, no differences existed in any of the inflammatory mediators (all p > 0.05). Performance on the MSFT was the only predictor of IL-6 (β = -0.291, p = 0.031), IL-1β (β = -0.405, p = 0.005), IL-10 (β = 0.325, p = 0.021) and fasted blood glucose (β = -0.545, p < 0.001) concentrations. Adiposity was the only predictor of plasma insulin concentration (β = 0.515, p < 0.001) and blood pressure (diastolic: β = 0.259, p = 0.042; mean arterial pressure: β = 0.322, p = 0.011).Conclusion: Enhanced performance on the MSFT, but not O2 peak, was associated with a favorable inflammatory profile in adolescents; whilst adiposity adversely affected plasma insulin, diastolic and mean arterial blood pressure. These findings demonstrate that enhancing performance on the MSFT and maintaining a healthy body composition are a potential therapeutic intervention for the attenuation of risk factors for cardio-metabolic diseases in adolescents.

Severity of COPD and its relationship with IL-10

BackgroundThe present study was designed to compare inflammatory and metabolic responses according to severity of airflow among patients with COPD and to verify the relationship between pulmonary function, body composition, metabolic and inflammatory profile. MethodsFifty-one patients with mild to very severe COPD were recruited and divided according lung function in Mild-moderate (GOLD 1–2) n= 21; Severe (GOLD 3) n=25 and Very severe (GOLD 4) n=5. Patients were submitted to assessments of lung function (spirometry), functional exercise capacity (6-min walk test), body composition (Octopolar bioelectrical impedance), metabolic profile (glucose, triglycerides, total cholesterol, HDL-cholesterol and albumin (colorimetric assay)) and inflammatory profile (cytokines: IL-6, IL-10, TNF-α and IL-15 (ELISA)). ResultsWe found that patients in GOLD 3 group had lower levels of IL-10, triglycerides, visceral fat area, and higher IL-6 and IL-6/IL-10 ratio when compared to GOLD 1–2 patients. Additionally, GOLD 1–2 group presented negative correlation between TNF-α and HDL cholesterol (p= .01) and positive correlation between IL-15 and FEV1/FVC (p=.01), while GOLD 3 group showed positive correlation between IL-6 and IL-10 (p< .01), IL-6 and total cholesterol (p<.01) and negative correlation between IL-10 and HDL-cholesterol (p=.01). ConclusionOur findings suggest that patients with severe COPD can exhibit compromised “inflammatory status”, characterized by higher IL6, IL-6/IL-10 ratio and lower IL-10 concentration. Furthermore, IL-10 seems to be an interesting cytokine to be investigated in this kind of patients.