Changes In Inflammatory Activity Research Articles

Understanding the Health Consequences of Children’s Exposure to Violence

Violence is a regular feature of children’s lives in the United States. In nationwide surveys, 37% of youth report being physically assaulted each year, and 24% report having an indirect exposure, e.g., a murder in their neighborhood. There is increasing evidence linking these childhood violence exposures with adverse health outcomes across the lifespan. Yet we know little about the mechanisms involved, and whether protective factors exist that confer resilience. In this presentation, I will discuss a series of studies that seek to fill these gaps in knowledge. The results suggest three conclusions. First, following a violence exposure, children’s monocytes show an upregulation of inflammatory activity, marked by increased responsivity to microbial challenge and decreased sensitivity to inhibitory signals. Second, these inflammatory changes are evident following both personal victimizations, e.g., being assaulted, and indirect experiences, e.g., when a murder occurs in a child’s neighborhood, but he/she has no connection to the victim. These findings suggest that even “vicarious” experiences may have health consequences. Finally, a brain network involved with self-regulation – the central executive network (CEN) – appears to protect youth from these changes. Specifically, among children with high functional connectivity of the CEN, the patterns described above are not evident – for them, violence does not portend changes in inflammatory activity, or in cardiovascular health.

Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound

BackgroundOptical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up.Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers.Methods1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses.ResultsOST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01).ConclusionsOST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort.Trial registrationGerman Registry of Clinical Trials, DRKS00016752

Use of serum amyloid A in equine medicine and surgery.

Serum amyloid A (SAA) has become an indispensable part of the management of equine patients in general practice and specialized hospital settings. Although several proteins possess acute phase properties in horses, the usefulness of SAA exceeds that of other acute phase proteins. This is due to the highly desirable kinetics of the equine SAA response. SAA concentrations exhibit a rapid and pronounced increase in response to inflammation and a rapid decline after the resolution of inflammation. This facilitates the detection of inflammatory disease and real-time monitoring of inflammatory activity. SAA may be used in all stages of patient management: (1) before diagnosis (to rule in/rule out inflammatory disease), (2) at the time of diagnosis (to assess the severity of inflammation and assist in prognostication), and (3) after diagnosis (to monitor changes in inflammatory activity in response to therapy, with relapse of disease, or with infectious/inflammatory complications). By assessing other acute phase reactants in addition to SAA, clinicians can succinctly stage inflammation. White blood cell counts and serum iron concentration change within hours of an inflammatory insult, SAA within a day, and fibrinogen within 2-3 days; the interrelationship of these markers thus indicates the duration and activity of the inflammatory condition. Much research on the equine SAA response and clinical use has been conducted in the last decade. This is the prerequisite for the evidence-based use of this analyte. However, still today, most published studies involve a fairly low number of horses. To obtain solid evidence for use of SAA, future studies should be designed with larger sample sizes.

Regulation of macrophage activation by S-Nitrosothiols following ozone-induced lung injury

Acute exposure to ozone causes oxidative stress, characterized by increases in nitric oxide (NO) and other reactive nitrogen species in the lung. NO has been shown to modify thiols generating S-nitrosothiols (SNOs); this results in altered protein function. In macrophages this can lead to changes in inflammatory activity which impact the resolution of inflammation. As SNO formation is dependent on the redox state of both the NO donor and the recipient thiol, the local microenvironment plays a key role in its regulation. This dictates not only the chemical feasibility of SNO formation but also mechanisms by which they may form. In these studies, we compared the ability of the SNO donors, ethyl nitrite (ENO), which targets both hydrophobic and hydrophilic thiols, SNO-propanamide (SNOPPM) which targets hydrophobic thiols, and S-nitroso-N-acetylcysteine. (SNAC) which targets hydrophilic thiols. to modify macrophage activation following ozone exposure. Mice were treated with air or ozone (0.8 ppm, 3 h) followed 1 h later by intranasal administration of ENO, SNOPPM or SNAC (1–500 μM) or appropriate controls. Mice were euthanized 48 h later. Each of the SNO donors reduced ozone-induced inflammation and modified the phenotype of macrophages both within the lung lining fluid and the tissue. ENO and SNOPPM were more effective than SNAC. These findings suggest that the hydrophobic SNO thiol pool targeted by SNOPPM and ENO plays a major role in regulating macrophage phenotype following ozone induced injury.

Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.

Inflammation and depression: Research designs to better understand the mechanistic relationships between depression, inflammation, cognitive dysfunction, and their shared risk factors

There is convergent evidence that the immune system is dysregulated in some depressed individuals. A psychoneuroimmunology-based understanding of depression is advancing rapidly; however, a question of fundamental importance is poorly understood: does inflammation play a causal role in the etiology of depression or are elevated inflammatory biomarkers a downstream effect of depressive behaviors? Although longitudinal studies suggest that the relationship between depression and inflammation is characterized by complex bidirectional associations, existing prospective, longitudinal research designs are poorly equipped to investigate the dynamic interplay of depression and inflammation that unfolds over a relatively short time period. In addition, the precise role played by multiple, shared, and overlapping risk factors (e.g., diet, adiposity, stress, sleep dysregulation) in the etiology of depression and a pro-inflammatory phenotype (or both) is poorly understood. In this manuscript, I highlight the benefits of research designs that (i) manipulate constructs of interest (depression/inflammation) using intervention or treatment designs and (ii) use intensive sampling approaches with an ultimate goal of better understanding the temporal sequence and causal relationships of depression, inflammation, cognitive dysfunction, and their shared risk factors. For instance, are improved depressive symptoms a downstream effect of changes in inflammatory activity caused by increases in exercise or, alternatively, are changes in inflammatory activity and depression sequelae of improvements in sleep quality caused by increases in exercise? Potential benefits of these research designs are discussed in terms of their contribution to a better understanding of the etiology of depression and a pro-inflammatory phenotype, their relevance to structural health inequalities, and better characterizing the heterogeneous clinical presentation of depression, particularly relating to the etiology of cognitive dysfunction in depression.

The effect of exercise therapy on inflammatory activity assessed by MRI in knee osteoarthritis: Secondary outcomes from a randomized controlled trial

ObjectiveThis study investigated the effect of exercise therapy on inflammatory activity in synovitis and bone marrow lesions (BMLs) assessed by magnetic resonance imaging (MRI) in patients with knee OA. Methods60 patients with knee OA were randomized 1:1 to 12 weeks of supervised exercise therapy 3 times/week (ET) or a no-attention control group (CG).Synovitis and BMLs were assessed with static MRI with and without contrast and with dynamic contrast enhanced MRI (DCE-MRI). DCE-MRI data was quantified using pixel-by-pixel methodology based on analysis of signal intensity curves. Pain was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses of covariance were used assessing group differences in changes from baseline to week 12. Results33 patients adhered to the protocol and had valid MRI and KOOS data (ET, n = 16, CG, n = 17). Statistically significant and clinically relevant group difference in favour of ET was seen in KOOS pain change (−11.7 points, 95%CI: −20.1 to −3.4). There were statistically significant group differences in DCE-MRI assessed synovitis in the anterior synovium with unchanged inflammatory activity in the ET group compared to the CG. There were no group differences in BMLs and static MRI. ConclusionInflammatory activity was unchanged, and pain was reduced in patients with knee OA adhering to 12 weeks of exercise therapy compared to a no-attention control group. The reduction in pain was not explained by changes in inflammatory activity. Overall, the results suggest that exercise is not harmful in knee OA.ClinicalTrials.gov number: NCT01545258.

SAT0571 OPTICAL SPECTRAL TRANSMISSION TO ASSESS THERAPY RESPONSE IN PATIENTS WITH ARTHRITIS: A COMPARATIVE STUDY WITH CLINICAL, LABORATORY AND ULTRASONOGRAPHIC ACTIVITY MARKERS.

Background:Valid assessment of disease activity leads to outcome improvement in patients with rheumatoid arthritis (RA) (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of RA patients (commercial device: HandScan - Hemics, The Netherlands) (2).Objectives:To our knowledge, there are no data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes during arthitis follow up.Thus, aims of this study were to examine the ability of OST to detect response to anti-inflammatory therapy in patients with arthritis and to explore OST associations with clinical, laboratory and ultrasonographic (US) activity markers.Methods:OST measurements were performed in patients with active arthritides of the wrist and finger joints before and after administration of glucocorticoids (GC), during a disease flare. For the same points in time (a and b) patients and healthy controls underwent clinical, laboratory and joint US [Grey Scale (GSUS) - Power Doppler (PDUS)] examinations. OST-values before and after therapy were subsequently compared with their corresponding DAS28- and US-values. The distributions of Delta-PDUS und OST-values between the two time points were compared by Bayesian statistics. Moreover, OST diagnostic performance was tested by Receiver Operating Characteristics (ROC).Results:We recruited 54 patients with active inflammatory arthritis: 39 RA, 4 gout, 7 peripheral spondylarthritides and 4 other miscellaneous arthritides (66.7% females) and 114 controls.Previous to therapy with GC, median OST was [OST(a):8.75(5.38-16.25, IQR)] and after therapy [OST(b):4.75(2.38-8.63, IQR)] (p&lt;0.05). Similarly, DAS28 dropped significantly after GC therapy [DAS28(a):5.12(4.33-6.10, IQR) vs. DAS28(b):3.85(3.40-4.82),p&lt;0.05)]. OST correlated moderately with PDUS at both time points: (a)rho=0.449and (b)rho=0.414, respectively (both;p&lt;0.01). Moreover, OST correlated significantly with swollen joint count at both time points (a)rho=0.379and (b)rho=0.382,p&lt;0.01respectively.OST and US performed similarly in the assessment of inflammatory changes caused by the administration of GC (same tendency in the change of OST values in83.2%of the cases). Furthermore, Bayesian statistic revealed no significant differences between OST and US for all 3 examined joint categories (MCP:p=0.81; PIP:p=0.74; wrists:p=0.60).In addition, ROC revealed that OST is a very good tool to distinguish patients with arthritis from healthy controls at both examination points [AUC(a):0.883(95% CI=0.83-0.94) and AUC(b):0.811(95% CI=0.74-0.881)].Conclusion:OST was able to assess response to therapy in arthritis patients comparable to US. Moreover, OST correlated with disease activity markers and could effectively differentiate between arthritis patients and controls. Therefore, OST could prove to be a valuable non-interventional time- and resource-saving diagnostic tool to assist arthritis monitoring.

ВЛИЯНИЕ ММСК И ГСК НА РЕПАРАТИВНУЮ РЕГЕНЕРАЦИЮ ПЕЧЕНИ В УСЛОВИЯХ ЕЕ ТОКСИЧЕСКОГО ПОВРЕЖДЕНИЯ

The aim of this study was to study the effect of combined MMSC and HSC transplantation on liver regeneration under conditions of toxic carbon tetrachloride damage. Materials and methods. The study was performed on white male mice with toxic liver damage by intraperitoneal administration of carbon tetrachloride at a dose of 50 µl per mouse once. An hour after modeling liver damage, placental MMSCs and HSCs were administered intravenously at a dose of 4 million cells/kg and 330 thousand cells/kg, respectively, suspended in 0.2 ml of 0.9% NaCl solution. Control group animals were given 0.9% NaCl solution-0.2 ml intravenously. On days 1, 3, and 7 after cell transplantation, changes in inflammatory activity in the liver were evaluated, and mitotic and apoptotic indices were determined. On the 7th day after the introduction of cells, the activity of DNA repair enzymes of the PARP family was analyzed. Results. Combined MMSC and HSC transplantation leads to a decrease in the index of inflammatory activity in the liver due to a decrease in necrosis, hepatocyte dystrophy, and a decrease in infiltration. As a result of the study, an increase in the activity of PARP repair enzymes was found, which led to a decrease in programmed cell death. Also, cotransplantation of MMSCs and HSCs was accompanied by increased mitotic activity of hepatocytes. Conclusion. Cotransplantation of MMSCs and HSCs under conditions of toxic liver damage reduces the inflammatory response, stimulates the mitotic activity of hepatocytes, and increases the activity of enzymes of the DNA repair system. Activation of the liver's reparative system, in turn, reduces the programmed death of hepatocytes.

Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease.

BACKGROUNDStudies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin (FC) and fecal lactoferrin (FL) in monitoring inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation to endoscopic scores, disease severity and affected intestinal surface has not been extensively investigated.AIMTo correlate FL, and for comparison white blood cell (WBC) and C-reactive protein (CRP), with endoscopic scores, disease extent and location in CD and UC.METHODSRetrospective analysis in 188 patients who had FL, CRP and WBC determined within 30 d of endoscopy. Disease location, disease extent (number of intestinal segments involved), disease severity (determined by endoscopic scores), timing of FL testing in relation to colonoscopy, as well as the use of effective fast acting medications (steroids and biologics) between colonoscopy and FL measurement, were recorded.RESULTSIn 131 CD and 57 UC patients, both CRP and FL - but not WBC - distinguished disease severity (inactive, mild, moderate, severe). In patients receiving fast-acting (steroids or biologics) treatment in between FL and colonoscopy, FL showed a higher correlation to endoscopic scores when tested before vs after the procedure (r = 0.596, P < 0.001, vs r = 0.285, P = 0.15 for the Simple Endoscopic Score for CD; and r = 0.402, P = 0.01 vs r = 0.054 P = 0.84 for Disease Activity Index). Finally, FL was significantly correlated with the diseased mucosal surface (colon-ileocolon > small bowel) and the number of inflamed colon segments.CONCLUSIONFL and CRP separated disease severity categories with FL showing lower discriminating P-values. FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure – this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels. FL can accurately and timely characterize intestinal inflammation in IBD.

Quantitative tracking of inflammatory activity at the peak and trough plasma levels of tofacitinib, a Janus kinase inhibitor, via in vivo 18 F-FDG PET.

To assess the capability of in vivo positron emission tomography (PET) using 18 F-fluorodeoxyglucose (18 F-FDG) to quantify changes in inflammatory activity in response to tofacitinib, a Janus kinase (JAK) inhibitor, over a timeframe of a few hours to few days in a preclinical model of rheumatoid arthritis (RA). Twenty-four mice with collagen-induced arthritis in the following groups were assessed: Group 1, where the changes in PET measures for the extremity joints were evaluated at the peak and trough plasma drug levels after administration of a single dose of tofacitinib (4hours apart); Group 2, where joint PET measures were assessed before treatment and after 6days of administration of a daily dose of tofacitinib; and group 3 (controls), where joint PET measures were derived from the same mice, 6days apart. At about peak plasma levels of the drug after a single tofacitinib administration, there was a reduction in PET measures compared to pretreatment values, suggesting decreased inflammatory activity. These measures were equivalent to those obtained after 6days of daily dosing by tofacitinib. However, PET measures at trough plasma levels of the drug from tofacitinib administration were significantly higher than those at peak plasma drug levels and equivalent to pretreatment measures. There were insignificant changes in PET measures for the control animals. 18 F-FDG PET can detect changes in inflammatory activity occurring in response to the JAK inhibitor tofacitinib: (a) during peak and trough plasma drug levels, that is within mere hours of treatment; and (b) over a span of days.

Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study

Objectives: Crohn’s disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity.Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn’s disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin.Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = −0.39; p = .009). Changes in C. leptum (R = −0.18, p = .23) and number of copies of the BCoAT gene (R = −0.12; p = .42) did not correlate with f-calprotectin.Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn’s disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.

Pediatric Patients With Steroid-Sensitive Nephrotic Syndrome Have Higher Expression of T Regulatory Lymphocytes in Comparison to Steroid-Resistant Disease.

Background and Aim: Idiopathic nephrotic syndrome (INS) is classified according to the response to drug therapy in steroid-sensitive (SS), steroid-dependent (SD), and steroid-resistant (SR) categories. Previous studies showed changes in inflammatory activity of subpopulations of lymphocytes in INS. This study aimed to compare SS and SR patients in regard to subpopulations of leukocytes, profile of regulatory lymphocytes, and migratory activity of lymphocyte subpopulations. Results obtained in INS patients were also compared to age and sex-matched healthy controls.Methods: This is a cross-sectional study including SS patients (n = 30), SR patients (n = 14), and controls (n = 10). Peripheral blood samples were withdrawn for ex-vivo leukocyte flow cytometry analysis.Results: Percentage of B-lymphocytes and natural killer (NK) cells were significantly reduced in SR patients when compared to controls, while the percentage of NKT cells were decreased in SS patients in comparison to controls. Percentages of CD4+ expressing FoxP3 and CTLA4 were significantly higher in SS patients in comparison to SR patients and controls. The expression of integrin CD18 on the surface of T lymphocytes (CD3+) was reduced in SS patients if compared to controls.Conclusion: This study found that SS INS patients have higher levels of regulatory T-lymphocytes and lower expression of adhesion molecules than SR patients.

Longitudinal changes of inflammatory biomarkers moderate the relationship between recent stressful life events and prospective symptoms of depression in a diverse sample of urban adolescents

This study investigated whether longitudinal changes in inflammatory physiology moderated the relationship between recent stressful life events and subsequent depressive symptoms in adolescence. A diverse sample of adolescents representative of an urban community (N = 129; Age at baseline = 12.5 years; 48.8% female; 55.0% African American) completed measures of stressful life events, depressive symptoms, and two annual blood draws (BD1 and BD2). Controlling for inflammatory activity at BD1, depression at BD1, demographics and the time between assessments, increases in interleukin-6 (IL-6; b = 0.878, p = .007) and C-reactive protein (CRP; b = 0.252, p = .024) from BD1 to BD2 interacted with recent stressful life events before BD1 to predict severity of depressive symptoms at BD2. Similar associations were evident for IL-6 (b = 2.074, p = .040) and CRP (b = 0.919, p = .050) when considering acute stressful life events that had occurred within the two weeks before the first blood collection. More frequent stressful life events before BD1 predicted significantly more severe depressive symptoms at BD2, but only for adolescents with moderate (50th percentile) and high (84th percentile) levels of IL-6 and CRP at BD2. In conclusion, adolescents who experienced both recent stressful life events and larger increases in inflammatory activity following these stressors were at increased risk for more severe depressive symptoms after approximately one year. The findings indicate that the interaction of stress and larger changes in inflammatory activity following these stressors are prognostic risk factors for depression severity in adolescents.

Fermented barley and soybean (BS) mixture enhances intestinal barrier function in dextran sulfate sodium (DSS)-induced colitis mouse model.

BackgroundInflammatory bowel disease (IBD) is characterized by chronic or relapsing immune system activation and inflammation within the gastrointestinal tract. The lack of safety and efficacy of standard therapies, the use of food supplements for managing IBD is increasing, and many studies have reported that various food supplements provide many beneficial effects for the IBD.MethodsThis study aimed to evaluate the anti-colitis effects of dietary supplementation with a fermented barley and soybean mixture (BS) on intestinal inflammation using a murine model of IBD. Female C57BL/6 mice were administered with either BS (100 and 200 mg/kg/day) or vehicle (PBS) control through oral gavages for 3 days and received 5% dextran sulfate sodium (DSS) drinking water to induce colitis. Mice body weight was measured every two days and disease activity index (DAI) score was determined on Day 15; mice were sacrificed and colons were analyzed by H & E staining and RT-PCR. We also measured intestinal barrier function in vitro using DSS-treated Caco-2 cells by assessing ZO-1 immunofluorescence staining and Western blotting and in vivo by measuring serum level of FITC-Dextran and by performing bacteria culture from mesenteric lymph nodes (MLN) extract. The gut microbiota was examined by real time PCR using fecal DNA.ResultsWe found that BS alleviated the severity of colitis in a DSS-induced colitis mouse model, and suppressed levels of pro-inflammatory cytokines in colonic tissue. Moreover, BS prevented epithelial barrier dysfunction, inducing an increase of tight junction protein levels in colonic tissues, BS also inhibited FITC-dextran permeability, and suppressed bacterial translocation to MLNs. In addition, BS increased the levels of Lactobacilli and Bacteroides, which have anti-inflammatory properties.ConclusionOur study suggests that BS has protective roles against inflammatory bowel disease through changes in inflammatory activity, tight junction protein expression, and gut microbiota composition in DSS-induced colitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1479-0) contains supplementary material, which is available to authorized users.

P.1.j.011 - Anterior cingulate serotonin 1B receptor binding is positively associated with inhibitory control and amygdala reactivity to aversive faces

There is convergent evidence that the immune system is dysregulated in some depressed individuals. A psychoneuroimmunology-based understanding of depression is advancing rapidly; however, a question of fundamental importance is poorly understood: does inflammation play a causal role in the etiology of depression or are elevated inflammatory biomarkers a downstream effect of depressive behaviors? Although longitudinal studies suggest that the relationship between depression and inflammation is characterized by complex bidirectional associations, existing prospective, longitudinal research designs are poorly equipped to investigate the dynamic interplay of depression and inflammation that unfolds over a relatively short time period. In addition, the precise role played by multiple, shared, and overlapping risk factors (e.g., diet, adiposity, stress, sleep dysregulation) in the etiology of depression and a pro-inflammatory phenotype (or both) is poorly understood. In this manuscript, I highlight the benefits of research designs that (i) manipulate constructs of interest (depression/inflammation) using intervention or treatment designs and (ii) use intensive sampling approaches with an ultimate goal of better understanding the temporal sequence and causal relationships of depression, inflammation, cognitive dysfunction, and their shared risk factors. For instance, are improved depressive symptoms a downstream effect of changes in inflammatory activity caused by increases in exercise or, alternatively, are changes in inflammatory activity and depression sequelae of improvements in sleep quality caused by increases in exercise? Potential benefits of these research designs are discussed in terms of their contribution to a better understanding of the etiology of depression and a pro-inflammatory phenotype, their relevance to structural health inequalities, and better characterizing the heterogeneous clinical presentation of depression, particularly relating to the etiology of cognitive dysfunction in depression.

Soluble ST2 is a sensitive clinical marker of ulcerative colitis evolution

BackgroundThe ST2/IL-33 pathway has been related to ulcerative colitis (UC), and soluble ST2 (sST2), to disease severity. We tested the potential usefulness of sST2 as a predictive marker of treatment response and patients’ outcome.MethodsTwenty-six patients with active UC were prospectively recruited and grouped according to an endoscopic score and therapy response. Colonoscopic biopsies were collected at baseline and 6 months or when patients showed clinical activity. The protocol was reinitiated in patients requiring rescue therapy. Blood and stool were collected at baseline, 1, 3, 6 and 12 months. Serum and mucosal ST2, and fecal calprotectin (FC) content were determined by ELISA and correlated to Mayo clinical and endoscopic subscore. Intestinal ST2 was evaluated by immunofluorescence. Wilcoxon signed rank test and Spearman correlations (Rs) were applied (p <0.05).ResultsFollow-up was completed in 24 patients. sST2 levels (median and range) varied from 173.5 [136.6–274.0] to 86.5 [54.6–133.2] in responders (p < 0.05), and 336.3 [211.0–403.2] to 385.3 pg/mL [283.4–517.3] in non-responders at baseline and 6 months, respectively. sST2 levels correlated with Mayo clinical and endoscopic subscore, mucosal ST2 and FC (Rs = 0.57, 0.66, 0.74 and 0.42, respectively; p < 0.0001) and showed a trend similar to that of FC in responders. Non-responders revealed an increased ST2 content, restricted to the lamina propria’s cellular infiltrate.ConclusionsConsecutive sST2 measurement to follow changes in inflammatory activity of UC patients who respond or not to treatment identifies sST2, like FC, as a useful biomarker in predicting clinical outcome of UC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0520-6) contains supplementary material, which is available to authorized users.

Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory.

Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19–64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-α, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-α, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease.

Changes in Inflammatory Activity after Glaucoma Filtration Surgery in Children with Chronic Anterior Uveitis

ABSTRACTPurpose: To evaluate changes in inflammatory activity over time in patients with juvenile idiopathic arthritis (JIA)-associated anterior uveitis after two different types of glaucoma surgery.Methods: Retrospective analysis of 32 patients with JIA who had trabeculectomy (TE, 21 eyes) or Ahmed glaucoma valve implantation (AGV, 11 eyes). Inflammatory activity and use of anti-inflammatory medication were evaluated 1 year prior to surgery and in the first, third, and fifth years after surgery.Results: In both groups IOP decreased significantly from pre-surgery to 2 years after surgery (TE, 31.1 ± 6.7 to 12.8 ± 6.1 mmHg, p<0.0001; AGV, 28.5 ± 8.5 to 14.9 ± 6.6 mmHg, p<0.001). In the TE group flare, anterior chamber cells, and uveitis activity decreased significantly after surgery, whereas with AGV there was no sustained reduction of flare.Conclusions: The degree of inflammation in JIA-associated uveitis is significantly reduced after trabeculectomy.

Divergent amygdalar and prefrontal cortex delayed inflammatory mediator responses to acute psychological stress exposure

There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. Therefore, the aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of inflammatory mediators across a wide temporal range, in key corticolimbic brain regions regulating stress (amygdala, hippocampus, hypothalamus, prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30 min or 2 h of acute restraint stress and protein levels were examined 0 h through 24 h post termination of 2 h of acute restraint stress using multiplex arrays and ELISAs. Here, we are the first to show an increase in cytokine protein levels in the amygdala following acute psychological stress, and decreases in most of the cytokines measured for the prefrontal cortex. Understanding these mechanisms will allow us to better understand how changes in inflammatory activity at the level of the amygdala and prefrontal cortex could lead to disruptions of the neuroendocrine–immune interface which could lead to insight into the co-pathogenesis of chronic inflammatory states and mood disorders.