Marker Of Inflammatory Activity Research Articles

Inadequate CD18 shedding and increased depletion of soluble CD18 contributes to inflammatory activity in spondyloarthritis (P5090)

Abstract Spondyloarthritis (SpA) is characterized by inflammation in the axial skeleton and entheses. Integrin adhesion molecules containing the CD18 chain are pivotal regulators of leukocyte extravasation from the blood into zones of inflammation. Recently, we showed that CD18 is shed from leukocytes forming a soluble form of CD18 (sCD18) in the blood. Here we show that plasma sCD18 is a marker of inflammatory activity in SpA. The plasma levels of sCD18 were decreased in SpA patients compared with healthy controls and showed inverse correlations with disease activity scores including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Remarkably, this situation could be simulated in vitro. Thus, the degree of CD18 shedding from SpA patient-derived PBMC correlated inversely with the BASDAI score. According to flow cytometric analyses, CD18 was primarily shed from intermediate (CD14++ CD16+) monocytes. In agreement with earlier reports identifying CD18 as a substrate for MMP-9, the concentration of this enzyme in the culture supernatants correlated with the sCD18 concentration. Also, sCD18 complexes adhered to TNFα-stimulated endothelial cells expressing high levels of ICAM-1 but not to unstimulated cells. Taken together, our data links alterations in plasma sCD18 and inflammatory activity in SpA. The low plasma level of sCD18 in SpA seems to be a combination of inadequate CD18 shedding and increased depletion of sCD18 potentially affecting leukocyte migration.

Abdominal adiposity is the main determinant of the C-reactive response to injury in subjects undergoing inguinal hernia repair

BackgroundObesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery.Methods102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP.ResultsAge and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response.ConclusionWaist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability.

P068 High expression level of the T cell potassium channel, KV1.3, is a novel diagnostic marker of inflammatory activity in patients with ulcerative colitis

P068 High expression level of the T cell potassium channel, KV1.3, is a novel diagnostic marker of inflammatory activity in patients with ulcerative colitis

Peripheral Blood Levels of Matrix and Inflammatory Mediators are Elevated in Tunisian Patients with Acute Coronary Syndromes

The aim of the present study was to investigate differences of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients admitted with acute coronary syndrome (ACS), in correlation with the widely accepted markers of inflammatory activity, C-reactive protein, fibrinogen, and white blood cell number. 315 patients with ACS (165 unstable angina pectoris/non-ST-elevation myocardial infarction, 150 ST-elevation myocardial infarction), 111 stable angina (SA) patients, and 296 control subjects were enrolled in the study. All biochemical analyses were carried out using a Hitachi 912 analyzer (Roche). Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in citrate plasma by ELISA methods. White blood cells (WBC) and fibrinogen were also determined. The plasma concentrations of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, C-reactive protein, fibrinogen, and white blood cells in patients with acute coronary syndrome were significantly elevated compared to the control group (p < 0.001). MMP-9/TIMP-1 ratio was significantly higher in SA and ACS patients (p < 0.001) than controls. Strong positive associations were observed between MMP-9 and TIMP-1 (r = 0.213, p < 0.01), MMP-9 and CRP (r = 0.103, p < 0.01), MMP-9 and fibrinogen (r = 0.299, p < 0.01), MMP-9 and WBC (r = 0.135, p < 0.01), TIMP-1 and CRP (r = 0.219, p < 0.01), TIMP-1 and Fibrinogen (r = 0.226, p < 0.01), TIMP-1 and WBC (r = 0.094, p < 0.1), CRP and fibrinogen (r = 0.158, p < 0.01), CRP and WBC (r = 0.156, p < 0.01, and finally between fibrinogen and WBC (r = 0.234, p < 0.01) in the patients with ACS. In conclusion, our observations suggest that ACS shows an increase in both remodeling and inflammation markers. In addition, the strong relationship with MMP-9 and inflammatory mediators such as CRP, fibrinogen, and WBC in ACS patients suggests that MMP-9 might be an additional marker and/or consequence of inflammatory components in ACS.

Forced exercise enhances functional recovery after focal cerebral ischemia in spontaneously hypertensive rats.

Caveolin is the principal protein of caveolae and has been implicated in the pathogenesis of cerebral ischemia. To investigate whether changed expression of caveolins has a pivotal role in focal cerebral ischemia, we induced middle cerebral artery occlusion (MCAo)-reperfusion and examined expression of caveolins, inflammatory activation markers, and mediators of autophagic cell death. We also treated MCAo rats with forced exercise to determine its effects on neurological outcome. Particularly, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to compare the effects of hypertension on focal cerebral ischemia. All MCAo groups showed neurological deficiencies, motor dysfunction, and disruption of balancing ability; however, these pathological changes were more severe in SHR than WKY rats. Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased. Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups. Forced exercise attenuated both molecular and behavioral changes in MCAo animals, but SHR rats showed delayed functional recovery and residual molecular changes when compared to WKY rats. These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

Elevated markers of inflammation and endothelial activation and increased counts of intermediate monocytes in adult survivors of childhood acute lymphoblastic leukemia

BackgroundAdult survivors of childhood malignancy are prone to accelerated atherogenesis and late cardiovascular complications. Plaque formation is initiated by recruitment of monocytes and T-cells into the intima, mediated by adhesion molecules and chemokines expressed by activated endothelial cells. AimTo assess markers of inflammatory activity, endothelial activation as well as monocyte heterogeneity in adult survivors of childhood acute lymphoblastic leukemia (ALL) who had been treated with chemotherapy without cranial irradiation. Methods and resultsWe studied 27 (age: 18–28 years) healthy survivors of childhood ALL and 20 controls (age: 20–31 years). Flow cytometry was used to identify monocyte subsets: classical CD14++CD16−, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes which were further characterized by their expression of HLA-DR and β2-integrins CD11b/CD18 and CD11c/CD18. In ALL survivors we found increased levels of pentraxin-3 (median [interquartile range]: 0.63 [0.36–0.94] vs. 0.40 [0.32–0.57] ng/ml; p=0.03), soluble vascular cell adhesion molecule-1 (687 [597–761] vs. 558 [534–702]ng/ml; p=0.02), osteoprotegerin (mean±SD: 5.24±1.00 vs. 4.42±1.34pmol/l; p=0.02) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (107.0±23.6 vs. 89.5±18.9pg/ml; p=0.01), whereas C-reactive protein, interleukin 6 and 18, TNF-α, monocyte chemotactic protein-1 and soluble intercellular adhesion molecule-1 were unchanged. Former ALL patients exhibited elevated counts of intermediate monocytes (6.3±4.0 vs. 4.3±1.5% of blood monocytes; p=0.03). CD11b/CD18 and CD11c/CD18 expression on intermediate monocytes tended to be higher in ALL survivors (1917±993 vs. 1396±673 MFI [median fluorescence intensity]; p=0.06 and 3883±1445 vs. 3185±645 MFI; p=0.05, respectively). ConclusionOur findings suggest chronic inflammatory activation and immune dysregulation in adult survivors of childhood ALL, which can translate into late cardiovascular morbidity.

The Role of Oxidative Stress in Anti-tumor Necrosis Factor Antibody Treatment in Crohn´s Disease

Administration of anti-tumor necrosis factor alpha antibodies [anti-TNF]-alpha represents a therapeutic approach aimed to diminish the effects of tumor necrosis factor [TNF]- alpha in Crohn's disease [CD]. Blockade of its action should be related to various changes including those in immune and inflammatory response. There is a growing body of experimental data to suggest that the chronically inflamed intestine may be subjected to considerable oxidative stress. The aim of this study was to study the impact of therapy with anti-TNF [infliximab] on Crohn's disease activity index [CDAI], markers of inflammatory activity and oxidative stress. Fourteen patients with active CD received 5mg/kg of infliximab in a single intravenous infusion. CDAI, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fibrinogen [FBG], alpha-1 antitrypsin [AAT], albumin [ALB], ceruloplasmin apoprotein [CP], ferroxidase activity of CP [FOACP], specific enzymatic activity of CP [SEACP] and conjugated dienes [DIE] were determined before treatment in month 0 [M 0], in 1st control period in month 1 [M 1] and in 2nd control period in month 5 [M 5] after treatment. In clinical activity a sustained significant decrease in CDAI was observed, with a significant drop in M 1, remaining in M 5. A significant decrease in ESR in M 1, accompanied by insignificantly reduced levels of CRP and FBG was present. During the further follow up in M 5 a slight increase of ESR, CRP and FBG was noticed. A significant decrease of AAT in M 1 was present; this decrease was followed by a significant increase in M 5. Ceruloplasmin apoprotein levels dropped in M 1, with further slight insignificant increase in M 5. A significant increase of ALB sustaining in M 5 was present. The levels of DIE slightly decreased in M 1 and significantly in M 5, together with the slight increase of the FOACP and SEACP in M 1 and significant increase in M 5. We conclude, that oxidative stress may be important in the pathogenesis and perpetuation of tissue injury in CD patients. The decreasing levels of DIE together with the increase of the FOCP and SEACP after infliximab treatment together with changes of markers of inflammatory activity, can participate in the improvement of clinical status of patients with CD.

190 Immunohistochemical Validation of [18f]-Fluorodeoxyglucose as a Novel Biomarker of Inflamed Vulnerable Carotid Plaque: A Sub-Study of the Canadian Atherosclerosis Imaging Network (CAIN)

Atherosclerosis is a leading cause of morbidity and mortality within Canada. ‘Vulnerable' rupture prone plaque is associated with pronounced inflammatory activity and increased density of macrophage cells. Macrophages have increased metabolic rates and require high-levels of energy for phagocytic activity. Therefore, the uptake of radiolabelled glucose or [18F]-fluorodeoxyglucose (18FDG) imaged with hybrid positron emission tomography (PET) and computed tomography (CT) may serve as a surrogate marker of inflammatory activity within plaque.

Bone turnover and inflammatory markers of bisphosphonate-related osteonecrosis of the jaw in female osteoporosis patients

ObjectiveThis study aimed to analyze the difference in biochemical markers of patients with osteoporosis taking bisphosphonates (BPs) who developed bisphosphonate-related osteonecrosis of the jaw (BRONJ) vs those who did not develop BRONJ. Patients & methodsForty-one BRONJ patients and 76 control patients who had been treated with alendronate or risedronate were investigated. Bone turnover markers [C-terminal telopeptide (CTX) and bone-specific alkaline phosphatase (bALP)] and inflammatory activity markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were evaluated. In BRONJ patients, radiographic severity and its relation with the serological data and BRONJ staging were analyzed. ResultsCTX and bALP level after the long-term BPs treatment in the control patients was similar to the level of the BRONJ patients at the time of diagnosis. The BRONJ patients showed a significantly higher ESR than the control patients with BPs. BRONJ score were not correlated with CTX and bALP. The severity of BRONJ in alendronate-treated group was strongly correlated with ESR and CRP. ConclusionsBone turnover markers such as serum CTX level has limitation in reflecting BRONJ status. Increased level of inflammatory markers in BRONJ patients implies the importance of inflammation in BRONJ progression.

Quantified terminal ileal motility during MR enterography as a potential biomarker of Crohn’s disease activity: a preliminary study

To compare quantified terminal ileal (TI) motility during MR enterography (MRE) with histopathological severity of acute inflammation in Crohn's disease. A total of 28 Crohn's patients underwent MRE and endoscopic TI biopsy. Axial and coronal TrueFISP, HASTE and post-gadolinium VIBE images were supplemented by multiple coronal TrueFISP cine motility sequences through the small bowel volume. TI motility index (MI) was quantified using validated software; an acute inflammation score (eAIS; 0-6) was assigned to the biopsy. Two observers qualitatively scored mural thickness, T2 signal, contrast enhancement and perimural oedema (0-3) to produce an activity score (aMRIs) based on anatomical MRI. The association among the MI, eAIS and aMRIs was tested using Spearman's rank correlation. Wilcoxon rank sum test compared motility in subjects with and without histopathological inflammation. Mean MI and mean eAIS were 0.27 (range 0.06-0.55) and 1.5 (range 0-5), respectively. There was a significant difference in MI between non-inflamed (mean 0.37, range 0.13-0.55) and inflamed (mean 0.19, range 0.06-0.44) TI, P = 0.002, and a significant negative correlation between MI and both eAIS (Rho = -0.52, P = 0.005) and aMRIs (R = -0.7, P < 0.001). Quantified TI motility negatively correlates with histopathological measures of disease activity and existing anatomical MRI activity biomarkers. • Magnetic resonance imaging is increasingly used to assess Crohn's disease. • MRI measurements can provide a quantitative assessment of small bowel motility. • MR enterography can grade Crohn's disease. • Small bowel motility can be used as a marker of inflammatory activity.

Mesenteric Transit Time Using Contrast-Enhanced Ultrasound (CEUS) Does Not Correlate with Disease Activity in Crohn’s Disease

Evaluation of mesenteric transit time (MTT) - measured by contrast-enhanced ultrasound - as a marker for inflammatory activity in Crohn's disease. The time of maximum enhancement of the contrast agent in the superior mesenteric artery and vein was determined visually and by software analysis. The MTT was calculated as the difference between these two time points. Findings were correlated with the Harvey-Bradshaw Index (HBI) using the Pearson correlation coefficient (r). In addition, a healthy control group was evaluated both in the fasting state and 1, 2, 3 and 4 hours postprandially. In 20 healthy controls the mean visual MTT during fasting was 9.76 ± 2.83 sec and decreased to a minimum 1 hour after the meal (6.6 ± 2.27 sec). 45 patients with Crohn's disease (9 males, 36 females, mean age 35 years) had a mean HBI of 5.9 ± 4.7 points. The mean software-based MTT of 9.76 ± 3.7 sec was significantly higher (p = 0.034) than the mean visual MTT of 8.22 ± 3.05 sec. The two figures correlated well (r = 0.72, p < 0.001). The HBI correlated neither with the visual (r = 0.14, p = 0.371) nor with the software-based (r = 0.16, p = 0.293) MTT. The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.

Assessment of wall inflammation and fibrosis in Crohn’s disease: value of T1-weighted gadolinium-enhanced MR imaging

MRI is increasingly advocated as a robust method for quantifying disease activity in Crohn's disease. In particular, T1-weighted gadolinium-enhanced imaging shows considerable promise as a marker of inflammatory activity. However, interpretation of the literature must be made with an understanding of (i) the technical limitations of T1-weighted acquisition protocols and enhancement measurements; (ii) differences in standards of reference for disease activity employed between published studies; and (iii) important underlying macro and micro vascular changes in Crohn's disease. This review will focus specifically on the value of T1-weighted gadolinium-enhanced imaging in the assessment of wall inflammation and fibrosis.

Small Bowel Motility as a Marker for Inflammatory Activity in MR Enterography of Crohn's Disease

Small Bowel Motility as a Marker for Inflammatory Activity in MR Enterography of Crohn's Disease

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics. Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed. Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p < 0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p < 0.01; eNose breathprint r = 0.84, p = 0.002) (MPO: four compounds, p < 0.01; eNose r = 0.72, p = 0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD. Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.

A novel in vitro model for preclinical testing of the hemocompatibility of intravascular stents according to ISO 10993-4

Subacute stent thrombosis, caused by undesired interactions between blood and the stent surface, is a major concern in the first few weeks following coronary artery stent implantation. The aim of this study was to establish a novel in vitro model for hemocompatibility testing of coronary artery stents according to ISO 10993-4. The model consists of a modified Chandler-Loop design with closed heparin-coated PVC Loops and a thermostated water bath. The tests were performed with anticoagulated human whole blood. After incubation in the loop, blood was analyzed for coagulation and inflammatory activation markers (TAT, β-TG, sP-selectin, SC5b-9 and PMN-elastase). Three different stent types with varying thrombogenicity were tested; statistically significant differences were found between the three stent types in measures of coagulation and platelet activation. The new Chandler-Loop model can be used as an alternative to animal and current in vitro models, especially for the determination of early events after stent implantation.

Levels of Pentraxin‐3 in Gingival Crevicular Fluid and Plasma in Periodontal Health and Disease

Pentraxins are classic mediators of inflammation and markers of acute-phase reactions. Pentraxin-3 (PTX3) is the first-identified long pentraxin and is believed to be a true independent indicator of disease activity. Although a classic pentraxin, C-reactive protein, and its association with various systemic diseases is well documented in the periodontal literature, there is no data on PTX3 to our knowledge. Forty participants (20 males and 20 females; age range: 23 to 50 years) were involved in the study. Participants were divided into three groups based on gingival index, probing depth, and clinical attachment level: the healthy group (group 1; n = 10), gingivitis group (group 2; n = 15), and periodontitis group (group 3; n = 15). Gingival crevicular fluid (GCF) and plasma samples collected from each subject were quantified for PTX3 levels using an enzyme-linked immunosorbent assay. In tandem with the disease progression from healthy to gingivitis to periodontitis, the mean PTX3 concentrations increased in GCF and plasma. However, GCF values were higher than plasma values. It was found that PTX3 concentration was highest in group 3 and lowest in group 1. PTX3 concentrations also correlated positively with periodontal parameters. GCF and plasma PTX3 concentrations correlated positively in all groups. However, within the limits of the present study, the differences in plasma PTX3 levels were not found to be statistically significant. Hence, GCF PTX3 values were considered a marker of inflammatory activity in periodontal disease. However, PTX3 deserves further consideration as a therapeutic target. Additional large-scale studies should be carried out to confirm positive correlations.

Detection of edema in porcine carotid arteries using t2-weighted cardiovascular magnetic resonance

Arterial wall inflammation destabilizes atherosclerotic plaques and makes them prone to rupture (1) so detection of inflammatory activity may therefore assist discrimination between unstable and stable plaques. Inflammation of the vessel wall prompts transport of excess fluid into the interstitial space and results in the formation of edema (2). Hence, edema located within the vessel wall can be used as a marker for inflammatory activity.

An Alternate Method of Classifying Allergic Bronchopulmonary Aspergillosis Based on High-Attenuation Mucus

Background and AimAllergic bronchopulmonary aspergillosis (ABPA) is classified radiologically based on the findings of central bronchiectasis (CB) and other radiologic features (ORF). However, the long-term clinical significance of these classifications remains unknown. We hypothesized that the immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the severity and clinical outcomes of ABPA with different radiological classifications.MethodsPatients were classified based on CT chest findings as: (a) serologic ABPA (ABPA-S) and ABPA-CB; (b) ABPA-S, ABPA-CB, and ABPA-CB-ORF; and, (c) ABPA-S, ABPA-CB and ABPA-CB-HAM. The clinical, spirometric and serological (total and A fumigatus specific IgE levels, eosinophil count) severity of the disease and clinical outcomes in various classifications were analyzed.ResultsOf the 234 (123 males, 111 females; mean age, 34.1 years) patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and 27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM classification, while in other classifications these findings were inconsistent. On multivariate analysis, the factors predicting frequent relapses were presence of HAM (OR 7.38; 95% CI, 3.21–17.0) and CB (OR 3.93; 95% CI, 1.63–9.48) after adjusting for ORF.ConclusionsThe classification scheme based on HAM most consistently predicts immunological severity in ABPA. Central bronchiectasis and HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should be employed in the radiological classification of ABPA.

The Lipocalins Retinol-Binding Protein-4, Lipocalin-2 and Lipocalin-Type Prostaglandin D2-Synthase Correlate with Markers of Inflammatory Activity, Alcohol Intake and Blood Lipids, But not with Insulin Sensitivity in Metabolically Healthy 58-year-Old Swedish Men

The lipocalins retinol-binding protein (RBP)-4, lipocalin-2 and lipocalin-type prostaglandin D-synthase (L-PGDS) have been suggested to mediate obesity-associated insulin resistance and other metabolic co-morbidities. The role of lipocalins is however controversial and it is unclear whether they have a physiological role in regulation of insulin sensitivity and metabolic function in clinically healthy humans. Therefore, we examined the correlations between serum levels of RBP-4, L-PGDS and lipocalin-2 and insulin sensitivity and other metabolic parameters in non-diabetic subjects selected to display variations in insulin sensitivity. 100 clinically healthy 58-year-old Swedish men were selected by stratified sampling among 818 screened subjects to represent quintiles of varying degrees of insulin sensitivity. Insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp method. Serum levels of lipocalins and cytokines were determined using antibody-based techniques. Serum lipids were measured by standardized laboratory methods. None of the measured lipocalins showed any correlations with insulin sensitivity. However, we found that lipocalin-2 and L-PGDS were correlated with each other, but not with RBP-4. Lipocalin-2 and L-PGDS were positively correlated with soluble TNF- receptors 1 and 2 and negatively with alcohol consumption and serum HDL. Further, lipocalin-2 was correlated with interleukin-6 whereas RBP-4 was negatively correlated with TNF-α. □These results suggest that RBP-4, lipocalin-2 and L-PGDS do not regulate insulin sensitivity in healthy men. Rather the expression levels of lipocalin-2 and L-PGDS, but not RBP-4, seemed to reflect inflammatory activity and were inversely correlated with alcohol intake and serum HDL levels.

Acute Stress–induced Increases in Exhaled Nitric Oxide in Asthma and Their Association with Endogenous Cortisol

psychosocial stress is known to influence the pathophysiology of asthma. Although stress has been linked to serum markers of inflammatory activity and exaggerated response to allergen challenge in asthma, few studies have examined inflammatory activity in the airways linked to psychosocial stress alone. Furthermore, although studies have demonstrated lower levels or reactivity of endogenous cortisol in asthma, the association with airway inflammatory activity in stress remains unexplored. we therefore studied airway inflammation and cortisol response to a standardized laboratory task inducing acute psychosocial stress. airway inflammation by the fraction of exhaled nitric oxide (FeNO) and saliva cortisol were sampled before and up to 45 minutes after experimental challenge with the Trier Social Stress Test in 20 adult patients with asthma and 19 healthy control subjects. Respiratory inductive plethysmography was used to control for changes in ventilatory activity that impact FeNO levels. FeNO levels were generally higher in patients with asthma than healthy control subjects and salivary cortisol levels were lower. Increases in cortisol levels were observed after the stress protocol in both groups (P < 0.001). FeNO levels at the time of peak cortisol increase after stress were significantly higher than before stress in both groups (P < 0.05). FeNO increases were independent of changes in ventilation. In patients with asthma, higher cortisol levels and stronger increases in cortisol after stress were significantly associated with smaller increases in FeNO (P < 0.05). acute psychosocial stress alone increases airway inflammatory markers and this increase is attenuated by stronger stress-related activity of the hypothalamic-pituitary-adrenal axis in asthma.