Local Inflammatory Markers Research Articles

Abstract 88: Pentraxin 3 in Coronary Artery Lesions in Kawasaki Disease

Although vascular inflammation is an important feature of Kawasaki disease (KD), the usefulness of local inflammatory markers as biomarkers for KD is unknown. Pentraxin 3 (PTX3), soluble lectin-like oxidized low density lipoprotein receptor 1 (sLOX-1) and matrix metraloproteinase-9 (MMP-9) are biomarkers of inflammation of vascular components. Objective: We tested whether plasma concentrations of PTX3, sLOX-1 or MMP-9 would be a useful biomarker for detecting high risk patient of coronary artery aneurysm (CAA) in KD and compared with serum level of interleukin-6 (IL-6) and IL-18. The ability of the assays to identify KD patients at risk for CAA was analyzed. Methods: PTX3, sLOX-1, MMP-9, IL-6 and IL-18 concentrations of 50 KD patients at different four clinical points were analyzed. Point A represented on admission; B, pre-IVIG; A+B, before IVIG; C, after IVIG; D, after fever resolution. Each concentration was compared with the rate of occurrence of CAA and IVIG unresponsiveness. Results: Each value was evaluated in 50 KD patients (2 with CAA, 48 without CAA). Three patients were treated without IVIG, 17 with one course of IVIG, and six with two IVIGs, two with three IVIGs, respectively. At the points A+B, C, D means for PTX3 were; 33.4, 11.7, 9.00 ng/ml, mean for MMP-9; 34.6, 19.2, 24.2 ng/ml, mean for sLOX-1; 3.82, 2.33, 2.25 ng/ml, respectively. Levels of PTX3 (p<0.001) and MMP-9 (p<0.05) were significantly higher in before IVIG than after IVIG; whereas levels of sLOX-1, as well as those of IL-6 and IL-18 were comparable between before and after IVIG. PTX3 were well correlated with IL-6 level (R2=0.73). Both cases with extraordinary high PTX3 levels at admission of 91.8 and 65.3 ng/ml were complicated with coronary artery aneurysms, even though they were treated by three courses of IVIG. The level of plasma PTX3 was significant related with the course numbers of IVIG (p<0.05). Conclusion: Levels of PTX3 and MMP-9 appear to be associated with clinical course of KD. Levels of PTX3 were correlated with the severity of disease; how many doses of IVIG enough to resolve fever. An extraordinary high PTX3 level might be suggestive of the existence of CAA. These data suggest that PTX3 can be a candidate biomarker for prediction of unresponsiveness and CAA formation in patients with KD.

New biomarkers in the selection of patients for talcage of pleural cavity in the palliative therapy of malign pleural exudate.

Chemical pleurodesis using videothoracoscopically applied powdered talc under general anaesthesia and selective pulmonary ventilation is the most effective method of palliative therapy for malign pleural exudate. Talc produces an intense systemic inflammatory reaction with the development of aseptic pleurisy. The result is obliteration of the pleural cavity provided there is an intense inflammatory reaction in the pleural cavity and good contact of both pleural leaves. The course of the adherence of pleural leaves can be followed using skiascopy. In routine practice, the course of local inflammatory markers is difficult to evaluate. Selection of suitable patients who will respond to this procedure is another principal obstacle of this surgical method. To evaluate the course of local inflammatory changes in the pleural cavity following application of talc and to quantify their dynamics. Selection of specific biomarkers to predict the intensity of inflammation in the pleural exudate for targeted selection of patients suitable for talcage was the second aim of this study. 114 patients were retrospectively divided into Group A (N1 = 98) or patients without relapse and Group B (N2 = 16), patients with relapse of exudate formation. The need for repeated thoracic punctures or drainage over the course of a 12-month monitoring period was a criterion of treatment failure. Quantification of the effusion was performed by ultrasonic examination over a one year observational period at 3-monthly intervals. The concentration of soluble CD163 scavenger receptor and soluble Apo/Fas molecule was determined in exudate by ELISA. Soluble receptors in the 2 groups differed significantly. Group B showed higher sCD163 levels before talcage (P0 = 0.00024), faster dynamic decline in 2 h (P2 = 0.0092) and in 24 h (P24 = 0.0087). During monitoring, decrease in group B was statistically significant at 2 h (P2 = 0.056) and at 24 hrs (P24 = 0.0066). This pilot study showed that high values of sCD163 and sApo/Fas in the pleural exudate can predict treatment failure. Unsuitable candidates for this type of therapy couldbe selected in this way.

Fraction of exhaled nitric oxide measurement as a biomarker in asthma and COPD compared with local and systemic inflammatory markers

BackgroundAsthma and COPD are characterized by chronic airway inflammation that results in chronic airway obstruction which is reversible in asthma and non-reversible or partially reversible in COPD. The differential diagnosis between reversible or irreversible airflow obstruction due to asthma or COPD is important in clinical practice because the prognosis and the response to treatment of the two diseases are different. Nitric oxide (NO) is produced by many cells within the respiratory tract. Endogenous NO may play an important signaling role in the physiological control of airway function and in the pathophysiology of airway diseases. Measurement of airway inflammation by means of FENO may be useful and convenient for asthma diagnosis, particularly when bronchial challenges and/or spirometric maneuvers cannot be correctly performed. The increase in the percentage of peripheral blood and sputum eosinophils was found in patients with asthma that correlated with the clinical severity of asthma and pulmonary function. Elevated levels of C-reactive protein (CRP) are established in COPD but, in asthma, the results have been inconsistent. The aim of the present study was to evaluate differences in local (airway) and systemic inflammatory markers among primary care patients with asthma and COPD using simple, rapid and easy to do tests. Subjects and methodsOne hundred and fifty patients and thirty control subjects were included in this study. They were divided into three groups, ninety asthmatic patients diagnosed clinically and physiologically as reversible airway obstruction (group I). Sixty COPD patients diagnosed by clinical, physiological and laboratory tests to have irreversible or partially reversible airway obstruction (group II). The third group is the control group with no airway obstruction (NAO) including thirty subjects. Pulmonary function tests, FENO, hs-CRP, blood and sputum eosinophil percentages were done to all subjects. ResultsFENO was positively correlated with all inflammatory markers in the asthmatic group with highly significant differences (p⩽.001) and negatively correlated with age, BMI and PFTs. In the COPD group there was a positive correlation between FENO with all inflammatory markers and PFT with highly significant differences (p⩽.001) with sputum and blood eosinophils and not significantly correlated with hs-CRP and PFT. ConclusionIt is concluded that there are significant differences in inflammatory patterns between asthma and COPD. FENO and hs-CRP had the highest ability to discriminate between patients with asthma and COPD.

Identification of local angiogenic and inflammatory markers in the menstrual blood of women with endometriosis

The aim of this study was to evaluate the presence of myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG), tumor necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral and menstrual blood in women with (n=10) and without (n=7) endometriosis. NAG and MPO activities were evaluated by enzymatic methods, whereas TNF-α and VEGF by immunoassay. No significant differences were found for these markers, neither in menstrual nor in peripheral blood between groups. Menstrual blood NAG (P=0.039) and MPO (P=0.0117) activities in the endometriosis group were significantly higher than in peripheral blood. NAG and MPO presented positive linear correlation in peripheral (P=0.07; r=0.641) and menstrual blood (P=0.01; r=0.603). These findings point to the existence of an increased local inflammatory activity in women with endometriosis.

Investigating the spill-over hypothesis: Analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma

Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis.Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables.Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥−0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin.In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.

THU0202 Changes in Serum C-Reactive Protein and Erythrocyte Sedimentation Rate do not Associate with Radiographic Progression in Patients with Knee Osteoarthritis: A 2 Years Follow-Up Study in the AMS-OA Cohort

ObjectivesTo examine the associations of elevated serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with radiographic progression in patients with established knee osteoarthritis (OA), over two-years.MethodsData from 186 patients...

Do inflammatory markers portend heterotopic ossification and wound failure in combat wounds?

After a decade of war in Iraq and Afghanistan, we have observed an increase in combat-related injury survival and a paradoxical increase in injury severity, mainly because of the effects of blasts. These severe injuries have a devastating effect on each patient's immune system resulting in massive upregulation of the systemic inflammatory response. By examining inflammatory mediators, preliminary data suggest that it may be possible to correlate complications such as wound failure and heterotopic ossification (HO) with distinct systemic and local inflammatory profiles, but this is a relatively new topic. We asked whether systemic or local markers of inflammation could be used as an objective means, independent of demographic and subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure (defined as wounds requiring surgical débridement after definitive closure, or wounds that were not closed or covered within 21 days of injury) in patients sustaining combat wounds. Two hundred combat wounded active-duty service members who sustained high-energy extremity injuries were prospectively enrolled between 2008 and 2012. Of these 200 patients, 189 had adequate followups to determine the presence or absence of HO, and 191 had adequate followups to determine the presence or absence of wound failure. In addition to injury-specific and demographic data, we quantified 24 cytokines and chemokines during each débridement. Patients were followed clinically for 6 weeks, and radiographs were obtained 3 months after definitive wound closure. Associations were investigated between these markers and wound failure or HO, while controlling for known confounders. The presence of an amputation (p < 0.001; odds ratio [OR], 6.1; 95% CI. 1.63-27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95% CI, 4.2-413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002-1.009), serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5-4.5), serum IL-12p70 (p = 0.01; OR, 0.49; 95% CI, 0.27-0.81), effluent IL-3 (p = 0.02; OR, 1.75; 95% CI, 1.2-2.9), and effluent IL-13 (p = 0.006; OR, 0.67; 95% CI, 0.50-0.87) were independently associated with HO formation. Injury Severity Score (p = 0.05; OR, 18; 95% CI, 5.1-87), wound surface area (p = 0.05; OR, 28.7; 95% CI, 1.5-1250), serum procalcitonin ([ProCT] (p = 0.03; OR, 1596; 95% CI, 5.1-1,758,613) and effluent IL-6 (p = 0.02; OR, 83; 95% CI, 2.5-5820) were independently associated with wound failure. We identified associations between patients' systemic and local inflammatory responses and wound-specific complications such as HO and wound failure. However, future efforts to model these data must account for their complex, time dependent, and nonlinear nature. Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Aspirin Challenge in Patients with Chronic Rhinosinusitis with Polyps Correlates with Local and Systemic Inflammatory Markers

Acetylsalicylic acid (ASA; aspirin) is a well-known inducer of pseudoallergic response in patients with chronic rhinosinusitis with polyps (CRSwPs). The mechanism that leads to this response remains unclear. This study was designed to measure and compare the local and systemic inflammatory response to aspirin challenge in patients with CRSwPs who develop either a nasobronchial response (NBR) or a nasal response (NR), and compare it with nonresponders (non-Rs). The three groups underwent nasal wash before ASA challenge, and inflammatory mediators were measured in the nasal wash as well as in serum. A total of 25 CRSwP patients were enrolled. The NBR patients (n = 13) had a significantly longer mean disease duration and a higher mean serum leukotriene E4 (LTE4) level than the NR (n = 6) and non-R (n = 6) patients (39.2 ± 9.7 months, 21 ± 8.8 months, and 22.8 ± 11.2 months, respectively, and 4221 ± 1205 pg/mL, 1430 ± 605 pg/mL, and 857 ± 461 pg/mL, respectively). The NBR and NR patients had a larger mean number of nasal eosinophils than the non-R group (52.8 ± 28.8 cells/μL, 47 ± 21.3 cells/μL, and 19.3 ± 13.4 cells/μL, respectively). The tryptase, albumin, nasal LTE4, and prostaglandin E2 levels were not significantly different between the three groups in any examined combination. The nasal eosinophil and serum LTE4 levels correlate with aspirin sensitivity.

Biomarkers of periodontitis and inflammation in ischemic stroke: A case-control study

Periodontitis is a common infectious disease associated with increased risk for ischemic stroke though presently unclear mechanisms. In a case-control study, we investigated salivary levels of four periodontal pathogens, as well as systemic and local inflammatory markers. The population comprised 98 patients with acute ischemic stroke (mean ± SD, 68.2 ± 9.7 yrs; 45.9% women) and 100 healthy controls (69.1 ± 5.2 yrs; 47.0% women). Patients were more often edentulous and had fewer teeth than controls (13.8 ± 10.8 versus 16.6 ± 10.1). After adjusting for stroke risk factors and number of teeth, controls had higher saliva matrix metalloproteinase-8 (MMP-8), myeloperoxidase (MPO), IL-1β, Aggregatibacter actinomycetemcomitans, and serum LPS activity levels. Patients had higher serum MMP-8 and MPO, and they were more often qPCR-positive for A. actinomycetemcomitans (37.9% versus 19.0%) and for ≥3 periodontopathic species combined (50.0% versus 33.0%). We conclude that controls more often had evidence of current periodontal infection with higher periodontal pathogen amount, endotoxemia, local inflammation and tissue destruction. Stroke patients more often had evidence of end-stage periodontitis with edentulism and missing teeth. They were more often carriers of several periodontopathic pathogens in saliva, especially A. actinomycetemcomitans. Additionally, inflammatory burden may contribute to high systemic inflammation associated with elevated stroke susceptibility.

Can Effluent Matrix Metalloproteinase 2 and Plasminogen Activator Inhibitor 1 be Used as Biomarkers of Peritoneal Membrane Alterations in Peritoneal Dialysis Patients?

Peritoneal effluent contains clinically relevant substances derived from intraperitoneal production or transperitoneal transport, or both. The glycoproteinase matrix metalloproteinase 2 (MMP-2) cleaves denatured collagen and complements other collagenases in the degradation of fibrillar collagens. Elevated intraperitoneal levels of plasminogen activator inhibitor 1 (PAI-1) have been demonstrated to be present in patients with intra-abdominal adhesions. The aim of the present study was therefore to investigate the potential for effluent MMP-2 and PAI-1 to be used as markers of the development of peritoneal alterations. In addition, MMP-2 was analyzed in previously frozen effluent samples from a uremic rat model, in which data concerning the severity of peritoneal fibrosis were available. This prospective, single-center cohort study included 86 incident peritoneal dialysis (PD) patients. All patients were treated solely with biocompatible dialysis solutions and underwent a standard peritoneal permeability analysis (SPA). The presence of local MMP-2 and PAI-1 production and the relationships between those markers and peritoneal transport parameters were analyzed. Furthermore, effluent interleukin 6 was analyzed as a marker of local inflammation. Median effluent levels of 21.4 ng/mL for MMP-2 and 0.9 ng/mL for PAI-1 were found. The median dialysate appearance rates were 218.8 ng/min for MMP-2 and 9.6 ng/min for PAI-1. Local peritoneal production averaged 90% of effluent MMP-2 concentration and 74% of effluent PAI-1 concentration. Furthermore, correlations between peritoneal transport parameters and MMP-2 and PAI-1 were observed. Longitudinal follow-up showed no change for MMP-2 (p = 0.37), but a tendency for PAI-1 to increase with the duration of PD (p < 0.001). In rats, a significant relationship was present between the extent of peritoneal fibrosis and the appearance rate of MMP-2 (r = 0.64, p = 0.03). The foregoing data illustrate the potential of effluent MMP-2 and PAI-1 as biomarkers of peritoneal modifications, especially fibrosis; however, the components of peritoneal transport and local production should be clearly distinguished in every patient.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.

Identification of local angiogenic and inflammatory markers in the menstrual blood of women with endometriosis

Evaluate the presence of inflammatory markers myeloperoxidase (MPO), N-acetylglucosaminidase (NAG), tumor necrosis factor alpha(TNF-α) and angiogenesis (vascular endothelial growth factor - VEGF) in peripheral and menstrual blood in women with and without endometriosis.

Electrophysiological correlation and prognostic impact of pentraxin 3 as a local inflammatory marker in atrial fibrillation

Electrophysiological correlation and prognostic impact of pentraxin 3 as a local inflammatory marker in atrial fibrillation

Does Limb Preconditioning Reduce Pain After Total Knee Arthroplasty? A Randomized, Double-blind Study

Total knee arthroplasty (TKA) can be associated with considerable postoperative pain. Ischemic preconditioning of tissue before inducing procedure-related underperfusion may reduce the postoperative inflammatory response, which further may reduce associated pain. In this prospective, randomized study, we aimed at evaluating the impact of ischemic preconditioning on postoperative pain at rest and during exercise; use of pain medication; levels of systemic prothrombotic and local inflammatory markers; and length of stay and achievement of physical therapy milestones. Sixty patients undergoing unilateral TKA under tourniquet were enrolled with half (N = 30) being randomized to an episode of limb preconditioning before induction of ischemia for surgery (tourniquet inflation). Pain scores, analgesic consumption, markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor [TNF]-α in periarticular drainage), and periarticular circumference were measured at baseline and during 2 days postoperatively. Changes in prothrombotic markers were evaluated. Patients in the preconditioning group had significantly less pain postoperatively at rest (mean difference = -0.71, 95% confidence interval [CI] = -1.40 to -0.02, p = 0.043) and with exercise (mean difference = -1.38, 95% CI = -2.32 to -0.44, p = 0.004), but showed no differences in analgesic consumption. No differences were seen between the study and the control group in terms of muscle oxygenation and intraarticular levels of IL-6 and TNF-α as well as levels of prothrombotic markers. No differences were found between groups in regard to hospitalization length and time to various physical therapy milestones. Ischemic preconditioning reduces postoperative pain after TKA, but the treatment effect size we observed with the preconditioning routine used was modest. Given the ease of this intervention, ischemic preconditioning may be considered as part of a multimodal analgesic strategy. However, more study into the impact of different preconditioning strategies, elucidation of mechanisms, safety profiles, and cost-effectiveness of this maneuver is needed.

FRI0258 Decreased tslp expression in labial salivary glands of patients with primary sjögren’s syndrome is associated with increased t and b cell inflammation and tissue destruction

BackgroundThymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory cytokine involved in Th2-mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently shown to lead...

SAT0172 Decreased expression of thymic stromal lymphopoietin in labial salivary glands of patients with primary sjögren’s syndrome is associated with local and systemic disease parameters

BackgroundThymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory IL-7 related cytokine involved in Th2 mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently...

MCP-1 in psoriatic patients: effect of biological therapy

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine locally and systemically augmented in psoriasis. A single nucleotide polymorphism in MCP-1 promoter region -2518A→G is associated with higher gene expression. Objective: The aim was to evaluate MCP-1 plasma level in psoriatic patients and to relate any association in plasmatic and cutaneous MCP-1 with clinical improvement due to biological drugs. Methods: Blood samples were obtained from: (i) 30 Caucasian patients with psoriasis and 10 controls, for determining MCP-1 plasma concentrations and -2518A→G polymorphism occurrence, (ii) 16 psoriatic patients treated by anti-tumor necrosis factor-α (TNF-α) adalimumab/etanercept or by anti-CD-11 efalizumab, before and after 2 months of treatment. Moreover, biopsies were performed on lesional skin of five patients treated with anti-TNF-α. MCP-1 plasma concentration and cutaneous expression were determined by ELISA and qRT-PCR. Results: MCP-1 plasma level was significantly increased in psoriatic patients. -2518A→G polymorphism was similarly distributed in patients and controls and unrelated to MCP-1 plasma level or to Psoriasis Area and Severity Index. All patients receiving biological drugs showed significant clinical improvement. Anti-TNF-α therapy moderately reduced MCP-1 plasma concentration and robustly decremented MCP-1 expression in lesional skin. Conclusion: MCP-1 should be a potential local inflammatory marker in psoriatic patients to assess disease severity and anti-TNF-α treatment efficacy.

Renal ischemia‐reperfusion (I/R) injury induces a rapid activation of local inflammatory markers and causes increased peritubular permeability.

Local cytokines were measured in renal hilar lymph and in cortex after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion. The effect of I/R on size selectivity for proteins in glomerular and peritubular capillaries were estimated using HPLC and mass spectrometry. Whereas all measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and approached control levels after 120 min reperfusion, the responses were differentiated. IL‐1beta, MCP‐1 and leptin were markedly increased in plasma before reperfusion, reflecting an extra renal response possibly induced by afferent renal nerve activity from the ischemic kidney. The cortical cytokine content also reached high levels before reperfusion suggesting proteolytic release of local stores. However, only TNF‐alpha showed increased lymph to plasma ratio (L/P&gt;;1) following 30 min reperfusion indicating release of mediators directly into the bloodstream in agreement with abundant cytokine staining of glomerular and peritubular capillaries. The cytokine levels were paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine indicating temporarily reduced size selectivity of both glomerular and peritubular capillaries. In conclusion, short time renal ischemia is a strong trigger for a local as well as systemic inflammatory reaction.

The Peroxisome Proliferator-activated Receptor γ Coactivator 1α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells

A persistent, low-grade inflammation accompanies many chronic diseases that are promoted by physical inactivity and improved by exercise. The beneficial effects of exercise are mediated in large part by peroxisome proliferator-activated receptor γ coactivator (PGC) 1α, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1α and the related PGC-1β on inflammatory cytokines upon stimulation of muscle cells with TNFα, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-κB signaling. Interestingly, PGC-1α and PGC-1β both reduced phoshorylation of the NF-κB family member p65 and thereby its transcriptional activation potential. Taken together, the data presented here show that the PGC-1 coactivators are able to constrain inflammatory events in muscle cells and provide a molecular link between metabolic and immune pathways. The PGC-1s therefore represent attractive targets to not only improve metabolic health in diseases like type 2 diabetes but also to limit the detrimental, low-grade inflammation in these patients.

The dynamics of selected local inflammatory markers to talc in the treatment of malignant pleural effusions

Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H₂Mg₃(SiO₃)₄) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in pleural fluid before the talc poudrage. This showed limited ability to create an adequate inflammatory response to external stimuli. This group also showed lower levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect of the treatment was not influenced by morphologic tumour type. No statistically significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.